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Lecce E, Bellini A, Greco G, Martire F, Scotto di Palumbo A, Sacchetti M, Bazzucchi I. Physiological mechanisms of neuromuscular impairment in diabetes-related complications: Can physical exercise help prevent it? J Physiol 2025. [PMID: 39898972 DOI: 10.1113/jp287589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/14/2025] [Indexed: 02/04/2025] Open
Abstract
Diabetes mellitus is a chronic disorder that progressively induces complications, compromising daily independence. Among these, diabetic neuropathy is particularly prevalent and contributes to substantial neuromuscular impairments in both types 1 and 2 diabetes. This condition leads to structural damage affecting both the central and peripheral nervous systems, resulting in a significant decline in sensorimotor functions. Alongside neuropathy, diabetic myopathy also contributes to muscle impairment and reduced motor performance, intensifying the neuromuscular decline. Diabetic neuropathy typically implicates neurogenic muscle atrophy, motoneuron loss and clustering of muscle fibres as a result of aberrant denervation-reinervation processes. These complications are associated with compromised neuromuscular junctions, where alterations occur in pre-synaptic vesicles, mitochondrial content and post-synaptic signalling. Neural damage is intensified by chronic hyperglycaemia and oxidative stress, exacerbating vascular dysfunction and reducing oxygen delivery. These complications imply a severe decline in neuromuscular performance, evidenced by reductions in maximal force and power output, rate of force development and muscle endurance. Furthermore, diabetes-related complications are compounded by age-related degenerative changes in long-term patients. Aerobic and resistance training offer promising approaches for managing blood glucose levels and neuromuscular function. Aerobic exercise promotes mitochondrial biogenesis and angiogenesis, supporting metabolic and cardiovascular health. Resistance training primarily enhances neural plasticity, muscle strength and hypertrophy, which are crucial factors for mitigating sarcopenia and preserving functional independence. This topical review examines current evidence on the physiological mechanisms underlying diabetic neuropathy and the potential impact of physical activity in counteracting this decline.
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Affiliation(s)
- Edoardo Lecce
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Alessio Bellini
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Giuseppe Greco
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Fiorella Martire
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Alessandro Scotto di Palumbo
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Massimo Sacchetti
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
| | - Ilenia Bazzucchi
- Laboratory of Exercise Physiology, Department of Movement, Human, and Health Sciences, University of 'Foro Italico', Rome, Italy
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Li J, Liu G, Zhang D, Zhang K, Cao C. Physiological Mechanisms Driving Microcirculatory Enhancement: the Impact of Physical Activity. Rev Cardiovasc Med 2025; 26:25302. [PMID: 40026510 PMCID: PMC11868893 DOI: 10.31083/rcm25302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 09/03/2024] [Accepted: 09/20/2024] [Indexed: 03/05/2025] Open
Abstract
Background Physical activity induces many beneficial adaptive changes to blood vessel microcirculation, ultimately improving both health and exercise performance. This positions it an effective non-pharmacological therapeutic approach for the rehabilitation of patients with various chronic diseases. Understanding the impact of different types of physical activities on microcirculation and elucidating their physiological mechanisms is crucial for optimizing clinical practice. Methods A comprehensive literature search was performed across multiple databases including PubMed, EBSCO, ProQuest, and Web of Science. Following a rigorous screening process, 48 studies were selected for inclusion into the study. Results Existing studies demonstrate that various forms of physical activity facilitate multiple positive adaptive changes at the microcirculation level. These include enhanced microvascular dilation-driven by endothelial cell factors and mechanical stress on blood vessels-as well as increased capillary density. The physiological mechanisms behind these improvements involve the neurohumoral regulation of endothelial cell factors and hormones, which are crucial for these positive effects. Physical activity also ameliorates inflammation markers and oxidative stress levels, upregulates the expression of silent information regulator 2 homolog 3, genes for hypoxia-inducible factors under hypoxic conditions, and induces favorable changes in multiple hemodynamic and hemorheological parameters. These structural and functional adaptations optimize myocardial blood flow regulation during exercise and improve both oxygen transport and utilization capacity, which are beneficial for the rehabilitation of chronic disease patients. Conclusions Our provides a reference for using physical activity as a non-pharmacological intervention for patients with chronic conditions. This framework includes recommendations on exercise types, intensity, frequency, and duration. Additionally, we summarize the physiological mechanisms through which physical activity improves microcirculation, which can inform clinical decision-making.
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Affiliation(s)
- Jianyu Li
- Division of Sports Science and Physical Education Tsinghua University, Tsinghua University, 100084 Beijing, China
| | - Guochun Liu
- Division of Sports Science and Physical Education Tsinghua University, Tsinghua University, 100084 Beijing, China
- College of Exercise Medicine, Chongqing Medical University, 400331 Chongqing, China
| | - Dong Zhang
- Institute of Artificial Intelligence in Sports, Capital University of Physical Education and Sports, 100091 Beijing, China
| | - Keying Zhang
- Department of Physical Education, Southeast University, 210012 Nanjing, Jiangsu, China
| | - Chunmei Cao
- Division of Sports Science and Physical Education Tsinghua University, Tsinghua University, 100084 Beijing, China
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Opazo-Díaz E, Montes-de-Oca-García A, Galán-Mercant A, Marín-Galindo A, Corral-Pérez J, Ponce-González JG. Characteristics of High-Intensity Interval Training Influence Anthropometrics, Glycemic Control, and Cardiorespiratory Fitness in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sports Med 2024; 54:3127-3149. [PMID: 39358495 DOI: 10.1007/s40279-024-02114-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2024] [Indexed: 10/04/2024]
Abstract
BACKGROUND Exercise is a non-pharmacological intervention for type 2 diabetes mellitus (T2DM), including moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). Despite diverse exercise protocol variations, the impact of these variations in HIIT on T2DM anthropometrics, glycemic control, and cardiorespiratory fitness (CRF) remains unclear. OBJECTIVE The aim was to examine the influence of HIIT protocol characteristics on anthropometrics, glycemic control, and CRF in T2DM patients and compare it to control (without exercise) and MICT. METHODS This review is registered in PROSPERO (CRD42021281398) and follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search, employing "high-intensity interval training" and "diabetes mellitus" in PubMed and Web of Science databases, with a "randomized controlled trial" filter, spanned articles up to January 2023. RESULTS Of 190 records, 29 trials were included, categorized by HIIT interval duration, training volume, and intervention period. Long-duration, high-volume, and long-term HIIT yields superior outcomes compared to control conditions for body mass, waist circumference, fasting plasma glucose, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), glycosylated hemoglobin (%HbA1c), and CRF. The findings favored HIIT over MICT for body mass in long-duration, high-volume, and short-term intervals (mean difference [MD] - 3.45, - 3.13, and - 5.42, respectively, all p < 0.05) and for CRF in long and medium work intervals and high volume (MD 1.91, 2.55, and 2.43, respectively, all p < 0.05), as well as in medium and long-term intervention (MD 2.66 and 2.21, respectively, all p < 0.05). Regardless of specific HIIT characteristics, no differences were found in the HIIT versus MICT comparison for glycemic control. CONCLUSIONS Specific HIIT protocol characteristics influence changes in anthropometrics, glycemic control, and CRF compared to control groups. However, compared to MICT, only longer duration, higher volume, and short-term HIIT improved body mass, waist circumference, and CRF in individuals with T2DM.
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Affiliation(s)
- Edgardo Opazo-Díaz
- ExPhy Research Group, Department of Physical Education, University of Cadiz, Puerto Real, Cádiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
- Exercise Physiology Lab, Physical Therapy Department, University of Chile, Santiago, Chile
| | - Adrián Montes-de-Oca-García
- ExPhy Research Group, Department of Physical Education, University of Cadiz, Puerto Real, Cádiz, Spain.
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain.
| | - Alejandro Galán-Mercant
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
- MOVE-IT Research Group, Department of Nursing and Physiotherapy, Faculty of Health Sciences, University of Cádiz, Cádiz, Spain
| | - Alberto Marín-Galindo
- ExPhy Research Group, Department of Physical Education, University of Cadiz, Puerto Real, Cádiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
| | - Juan Corral-Pérez
- ExPhy Research Group, Department of Physical Education, University of Cadiz, Puerto Real, Cádiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain
| | - Jesús Gustavo Ponce-González
- ExPhy Research Group, Department of Physical Education, University of Cadiz, Puerto Real, Cádiz, Spain.
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), Cádiz, Spain.
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Lav Madsen P, Sejersen C, Nyberg M, Sørensen MH, Hellsten Y, Gaede P, Bojer AS. The cardiovascular changes underlying a low cardiac output with exercise in patients with type 2 diabetes mellitus. Front Physiol 2024; 15:1294369. [PMID: 38571722 PMCID: PMC10987967 DOI: 10.3389/fphys.2024.1294369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Accepted: 02/19/2024] [Indexed: 04/05/2024] Open
Abstract
The significant morbidity and premature mortality of type 2 diabetes mellitus (T2DM) is largely associated with its cardiovascular consequences. Focus has long been on the arterial atheromatosis of DM giving rise to early stroke and myocardial infarctions, whereas less attention has been given to its non-ischemic cardiovascular consequences. Irrespective of ischemic changes, T2DM is associated with heart failure (HF) most commonly with preserved ejection fraction (HFpEF). Largely due to increasing population ages, hypertension, obesity and T2DM, HFpEF is becoming the most prevalent form of heart failure. Unfortunately, randomized controlled trials of HFpEF have largely been futile, and it now seems logical to address the important different phenotypes of HFpEF to understand their underlying pathophysiology. In the early phases, HFpEF is associated with a significantly impaired ability to increase cardiac output with exercise. The lowered cardiac output with exercise results from both cardiac and peripheral causes. T2DM is associated with left ventricular (LV) diastolic dysfunction based on LV hypertrophy with myocardial disperse fibrosis and significantly impaired ability for myocardial blood flow increments with exercise. T2DM is also associated with impaired ability for skeletal muscle vasodilation during exercise, and as is the case in the myocardium, such changes may be related to vascular rarefaction. The present review discusses the underlying phenotypical changes of the heart and peripheral vascular system and their importance for an adequate increase in cardiac output. Since many of the described cardiovascular changes with T2DM must be considered difficult to change if fully developed, it is suggested that patients with T2DM are early evaluated with respect to their cardiovascular compromise.
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Affiliation(s)
- Per Lav Madsen
- Department Cardiology, Herlev-Gentofte Hospital, Copenhagen University, Copenhagen, Denmark
- Department Clinical Medicine, Copenhagen University, Copenhagen, Denmark
- The August Krogh Section for Human Physiology, Department Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark
| | - Casper Sejersen
- The August Krogh Section for Human Physiology, Department Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark
- Department of Anaesthesia, Rigshospitalet, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
| | - Michael Nyberg
- Department Kidney and Vascular Biology, Global Drug Discovery, Novo Nordisk, Copenhagen, Denmark
| | | | - Ylva Hellsten
- The August Krogh Section for Human Physiology, Department Nutrition, Exercise and Sports, Copenhagen University, Copenhagen, Denmark
| | - Peter Gaede
- Department Endocrinology, Slagelse-Næstved Hospital, Copenhagen, Denmark
| | - Annemie Stege Bojer
- Department Cardiology, Herlev-Gentofte Hospital, Copenhagen University, Copenhagen, Denmark
- Department Endocrinology, Slagelse-Næstved Hospital, Copenhagen, Denmark
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Ashcroft SP, Stocks B, Egan B, Zierath JR. Exercise induces tissue-specific adaptations to enhance cardiometabolic health. Cell Metab 2024; 36:278-300. [PMID: 38183980 DOI: 10.1016/j.cmet.2023.12.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2023] [Revised: 10/06/2023] [Accepted: 12/05/2023] [Indexed: 01/08/2024]
Abstract
The risk associated with multiple cancers, cardiovascular disease, diabetes, and all-cause mortality is decreased in individuals who meet the current recommendations for physical activity. Therefore, regular exercise remains a cornerstone in the prevention and treatment of non-communicable diseases. An acute bout of exercise results in the coordinated interaction between multiple tissues to meet the increased energy demand of exercise. Over time, the associated metabolic stress of each individual exercise bout provides the basis for long-term adaptations across tissues, including the cardiovascular system, skeletal muscle, adipose tissue, liver, pancreas, gut, and brain. Therefore, regular exercise is associated with a plethora of benefits throughout the whole body, including improved cardiorespiratory fitness, physical function, and glycemic control. Overall, we summarize the exercise-induced adaptations that occur within multiple tissues and how they converge to ultimately improve cardiometabolic health.
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Affiliation(s)
- Stephen P Ashcroft
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Ben Stocks
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Brendan Egan
- School of Health and Human Performance, Dublin City University, Dublin, Ireland
| | - Juleen R Zierath
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Integrative Physiology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
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Cavalli NP, de Mello MB, Righi NC, Schuch FB, Signori LU, da Silva AMV. Effects of high-intensity interval training and its different protocols on lipid profile and glycaemic control in type 2 diabetes: A meta-analysis. J Sports Sci 2024; 42:333-349. [PMID: 38531052 DOI: 10.1080/02640414.2024.2330232] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2023] [Accepted: 03/07/2024] [Indexed: 03/28/2024]
Abstract
This meta-analysis of randomised clinical trials aimed to compare the effects of high-intensity interval training (HIIT) and its different protocols versus moderate-intensity continuous training (MICT) and/or control on total cholesterol, HDL, LDL, triglycerides, HbA1c levels, and fasting glucose in individuals with type 2 diabetes mellitus (T2DM). The search strategy was performed in PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Web of Science, Sport DISCUS, and PEDro, until January 2023. A total of 31 studies (1092 individuals) were included. When compared to control, HIIT decreased total cholesterol by -0.31 mmol/L (95% CI -0.49; -0.12), LDL by -0.31 mmol/L (95% CI -0.49; -0.12), triglycerides by -0.27 mmol/L (95% CI -0.33; -0.2), HbA1c by -0.75% (95% CI -0.97; -0.53), fasting glucose by -1.15 mmol/L (95% CI -1.44; -0.86), and increased HDL by 0.24 mmol/L (95% CI 0.06; 0.42). No difference was found in the comparison between HIIT versus MICT for any of the outcomes analysed, however subgroup analysis showed that a moderate-interval (>30s to < 2 min) and moderate-term (>4 to < 12 weeks) HIIT protocol reduced total cholesterol, when compared to MICT. HIIT is able to improve lipid profile and glycaemic control in T2DM individuals, and specific protocols can be recommended for improving total cholesterol levels.
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Affiliation(s)
- Nandiny Paula Cavalli
- Postgraduate Program in Movement Sciences and Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Mariana Brondani de Mello
- Postgraduate Program in Functional Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Natiele Camponogara Righi
- Postgraduate Program in Rehabilitation Sciences, Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Felipe Barreto Schuch
- Department of Sport Methods and Techniques, Postgraduate Program in Movement Sciences and Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Luis Ulisses Signori
- Department of Physiotherapy and Rehabilitation, Postgraduate Program in Movement Sciences and Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Antônio Marcos Vargas da Silva
- Department of Physiotherapy and Rehabilitation, Postgraduate Program in Movement Sciences and Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
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Arrieta-Leandro MC, Moncada-Jiménez J, Morales-Scholz MG, Hernández-Elizondo J. The effect of chronic high-intensity interval training programs on glycaemic control, aerobic resistance, and body composition in type 2 diabetic patients: a meta-analysis. J Endocrinol Invest 2023; 46:2423-2443. [PMID: 37454031 DOI: 10.1007/s40618-023-02144-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 06/18/2023] [Indexed: 07/18/2023]
Abstract
BACKGROUND Type 2 diabetes is an increasing health problem worldwide. HIIT has been proposed as an exercise alternative to be part of integral type 2 diabetes treatment. OBJECTIVE The aim of this meta-analysis was to determine the effect of different types of chronic HIIT on glycaemic control, aerobic resistance, and body composition in individuals above 18 years with T2D. DESIGN This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and was registered with PROSPERO on November 21st, 2021. DATA SOURCES A systematic literature search of the following databases: EbscoHost (Academic Search Ultimate, Fuente Académica Plus, MEDline and SportDiscus), Web of Science, PubMed, and EMBASE between April of 2021 and April of 2023 was conducted. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Eligibility criteria included (1) participants aged ≥ 18 years with a diagnosis of type 2 diabetes, (2) an HIIT protocol with detailed description, (3) control group and/or continuous aerobic training comparison group, (4) report of pre-test and post-test values for at least one of the studied variables (from glycaemic control, aerobic resistance, and/or body composition), and (5) experimental or quasi-experimental intervention design. ANALYSES Meta-analysis was made by a pre-post-test between-group analysis following the inverse variance heterogeneity model for each variable, and then, a subgroup analysis by type of HIIT was conducted. RESULTS Of the 2817 records obtained, 180 records were included for meta-analysis. Significant improvements were found in the most part of the variables when HIIT was compared to control group, while fat-free mass kept without changes. HIIT vs. continuous aerobic training results showed and advantage in favor of HIIT for fasting blood glycemia. Subgroup analysis refers a possible advantage of SI-HIIT and SIT-HIIT in the improvement of fasting glycemia and SIT-HIIT advantage in HOMA 1-IR decrease. CONCLUSIONS HIIT improves glycaemic control, aerobic resistance, and % fat and waist circumference, and kept fat-free mass unchanged in individuals with T2D. SI-HIIT and SIT-HIIT could be better than the other types of HIIT. HIIT benefit is similar to continuous aerobic training except for fasting blood glycemia.
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Affiliation(s)
- M C Arrieta-Leandro
- School of Physical Education and Sports, University of Costa Rica, San Jose, Costa Rica.
| | - J Moncada-Jiménez
- School of Physical Education and Sports, University of Costa Rica, San Jose, Costa Rica
- Human Movement Sciences Research Center (CIMOHU), University of Costa Rica, San Jose, Costa Rica
| | - M G Morales-Scholz
- School of Physical Education and Sports, University of Costa Rica, San Jose, Costa Rica
- Human Movement Sciences Research Center (CIMOHU), University of Costa Rica, San Jose, Costa Rica
| | - J Hernández-Elizondo
- School of Physical Education and Sports, University of Costa Rica, San Jose, Costa Rica
- Human Movement Sciences Research Center (CIMOHU), University of Costa Rica, San Jose, Costa Rica
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Kissane RWP, Hauton D, Tickle PG, Egginton S. Skeletal muscle adaptation to indirect electrical stimulation: divergence between microvascular and metabolic adaptations. Exp Physiol 2023; 108:891-911. [PMID: 37026596 PMCID: PMC10988499 DOI: 10.1113/ep091134] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 03/15/2023] [Indexed: 04/08/2023]
Abstract
NEW FINDINGS What is the central question of this study? Can we manipulate muscle recruitment to differentially enhance skeletal muscle fatigue resistance? What is the main finding and its importance? Through manipulation of muscle activation patterns, it is possible to promote distinct microvascular growth. Enhancement of fatigue resistance is closely associated with the distribution of the capillaries within the muscle, not necessarily with quantity. Additionally, at the acute stages of remodelling in response to indirect electrical stimulation, the improvement in fatigue resistance appears to be primarily driven by vascular remodelling, with metabolic adaptation of secondary importance. ABSTRACT Exercise involves a complex interaction of factors influencing muscle performance, where variations in recruitment pattern (e.g., endurance vs. resistance training) may differentially modulate the local tissue environment (i.e., oxygenation, blood flow, fuel utilization). These exercise stimuli are potent drivers of vascular and metabolic change. However, their relative contribution to adaptive remodelling of skeletal muscle and subsequent performance is unclear. Using implantable devices, indirect electrical stimulation (ES) of locomotor muscles of rat at different pacing frequencies (4, 10 and 40 Hz) was used to differentially recruit hindlimb blood flow and modulate fuel utilization. After 7 days, ES promoted significant remodelling of microvascular composition, increasing capillary density in the cortex of the tibialis anterior by 73%, 110% and 55% for the 4 Hz, 10 and 40 Hz groups, respectively. Additionally, there was remodelling of the whole muscle metabolome, including significantly elevated amino acid turnover, with muscle kynurenic acid levels doubled by pacing at 10 Hz (P < 0.05). Interestingly, the fatigue index of skeletal muscle was only significantly elevated in 10 Hz (58% increase) and 40 Hz (73% increase) ES groups, apparently linked to improved capillary distribution. These data demonstrate that manipulation of muscle recruitment pattern may be used to differentially expand the capillary network prior to altering the metabolome, emphasising the importance of local capillary supply in promoting exercise tolerance.
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Affiliation(s)
- Roger W. P. Kissane
- Department of Musculoskeletal & Ageing Science, Faculty of Health & Life SciencesUniversity of LiverpoolLiverpoolUK
- School of Biomedical Sciences, Faculty of BiosciencesUniversity of LeedsLeedsUK
| | - David Hauton
- Metabolomics Research Group, Department of ChemistryUniversity of OxfordOxfordUK
| | - Peter G. Tickle
- School of Biomedical Sciences, Faculty of BiosciencesUniversity of LeedsLeedsUK
| | - Stuart Egginton
- School of Biomedical Sciences, Faculty of BiosciencesUniversity of LeedsLeedsUK
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Kourek C, Karatzanos E, Raidou V, Papazachou O, Philippou A, Nanas S, Dimopoulos S. Effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in type 2 diabetes: A systematic review. World J Cardiol 2023; 15:184-199. [PMID: 37124974 PMCID: PMC10130888 DOI: 10.4330/wjc.v15.i4.184] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 02/22/2023] [Accepted: 03/29/2023] [Indexed: 04/20/2023] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) is a chronic metabolic syndrome characterized by insulin resistance and hyperglycemia that may lead to endothelial dysfunction, reduced functional capacity and exercise intolerance. Regular aerobic exercise has been promoted as the most beneficial non-pharmacological treatment of cardiovascular diseases. High intensity interval training (HIIT) seems to be superior than moderate-intensity continuous training (MICT) in cardiovascular diseases by improving brachial artery flow-mediated dilation (FMD) and cardiorespiratory fitness to a greater extent. However, the beneficial effects of HIIT in patients with T2DM still remain under investigation and number of studies is limited. AIM To evaluate the effectiveness of high intensity interval training on cardiorespiratory fitness and endothelial function in patients with T2DM. METHODS We performed a search on PubMed, PEDro and CINAHL databases, selecting papers published between December 2012 and December 2022 and identified published randomized controlled trials (RCTs) in the English language that included community or outpatient exercise training programs in patients with T2DM. RCTs were assessed for methodological rigor and risk of bias via the Physiotherapy Evidence Database (PEDro). The primary outcome was peak VO2 and the secondary outcome was endothelial function assessed either by FMD or other indices of microcirculation. RESULTS Twelve studies were included in our systematic review. The 12 RCTs resulted in 661 participants in total. HIIT was performed in 310 patients (46.8%), MICT to 271 and the rest 80 belonged to the control group. Peak VO2 increased in 10 out of 12 studies after HIIT. Ten studies compared HIIT with other exercise regimens (MICT or strength endurance) and 4 of them demonstrated additional beneficial effects of HIIT over MICT or other exercise regimens. Moreover, 4 studies explored the effects of HIIT on endothelial function and FMD in T2DM patients. In 2 of them, HIIT further improved endothelial function compared to MICT and/or the control group while in the rest 2 studies no differences between HIIT and MICT were observed. CONCLUSION Regular aerobic exercise training has beneficial effects on cardiorespiratory fitness and endothelial function in T2DM patients. HIIT may be superior by improving these parameters to a greater extent than MICT.
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Affiliation(s)
- Christos Kourek
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, Athens 10676, Greece
- Department of Cardiology, 417 Army Share Fund Hospital of Athens, Athens 11521, Greece
| | - Eleftherios Karatzanos
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, Athens 10676, Greece
| | - Vasiliki Raidou
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, National and Kapodistrian University of Athens, Athens 10676, Greece
| | - Ourania Papazachou
- Department of Cardiology, "Helena Venizelou" Hospital, Athens 10676, Greece
| | - Anastassios Philippou
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, Athens 10676, Greece
- Department of Physiology, School of Medicine, National and Kapodistrian University of Athens, Athens 11527, Greece
| | - Serafim Nanas
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, Athens 10676, Greece
| | - Stavros Dimopoulos
- Clinical Ergospirometry, Exercise and Rehabilitation Laboratory, 1 Critical Care Medicine Department, Evangelismos Hospital, Athens 10676, Greece
- Cardiac Surgery Intensive Care Unit, Onassis Cardiac Surgery Center, Athens 17674, Greece.
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Ozemek C, Arena R, Rouleau CR, Campbell TS, Hauer T, Wilton SB, Stone J, Laddu D, Williamson TM, Liu H, Chirico D, Austford LD, Aggarwal S. Long-Term Maintenance of Cardiorespiratory Fitness Gains After Cardiac Rehabilitation Reduces Mortality Risk in Patients With Multimorbidity. J Cardiopulm Rehabil Prev 2023; 43:109-114. [PMID: 36203224 DOI: 10.1097/hcr.0000000000000734] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/25/2023]
Abstract
PURPOSE The objective of this study was to characterize the impact of multimorbidity and cardiorespiratory fitness (CRF) on mortality in patients completing cardiac rehabilitation (CR). METHODS This cohort study included data from patients with a history of cardiovascular disease (CVD) completing a 12-wk CR program between January 1996 and March 2016, with follow-up through March 2017. Patients were stratified by the presence of multimorbidity, which was defined as having a diagnosis of ≥2 noncommunicable diseases (NCDs). Cox regression analyses were used to evaluate the effects of multimorbidity and CRF on mortality in patients completing CR. Symptom-limited exercise tests were completed at baseline, immediately following CR (12 wk), with a subgroup completing another test at 1-yr follow-up. Peak metabolic equivalents (METs) were determined from treadmill speed and grade. RESULTS Of the 8320 patients (61 ± 10 yr, 82% male) included in the analyses, 5713 (69%) patients only had CVD diagnosis, 2232 (27%) had CVD+1 NCD, and 375 (4%) had CVD+≥2 NCDs. Peak METs at baseline (7.8 ± 2.0, 6.9 ± 2.0, 6.1 ± 1.9 METs), change in peak METs immediately following CR (0.98 ± 0.98, 0.83 ± 0.95, 0.76 ± 0.95 METs), and change in peak METs 1 yr after CR (0.98 ± 1.27, 0.75 ± 1.17, 0.36 ± 1.24 METs) were different ( P < .001) among the subgroups. Peak METs at 12 wk and the presence of coexisting conditions were each predictors ( P < .001) of mortality. Improvements in CRF by ≥0.5 METS from baseline to 1-yr follow-up among patients with or without multimorbidity were associated with lower mortality rates. CONCLUSION Increasing CRF by ≥0.5 METs improves survival regardless of multimorbidity status.
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Affiliation(s)
- Cemal Ozemek
- Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago (Drs Ozemek, Arena, and Laddu); TotalCardiology Research Network, Calgary, Canada (Drs Arena, Rouleau, Campbell, Wilton, Stone, Chirico, and Aggarwal and Ms Austford); TotalCardiology™ Rehabilitation, Calgary, Canada (Drs Rouleau and Aggarwal and Ms Hauer); Departments of Psychology (Drs Rouleau, Campbell, and Aggarwal and Ms Williamson), Community Health Sciences (Dr Liu), and Kinesiology (Dr Chirico), University of Calgary, Calgary, Canada; and Libin Cardiovascular Institute, University of Calgary, Calgary, Canada (Drs Wilton, Stone, and Liu)
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11
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Lilja M, Moberg M, Apró W, Martínez-Aranda LM, Rundqvist H, Langlet B, Gustafsson T, Lundberg TR. Limited effect of over-the-counter doses of ibuprofen on mechanisms regulating muscle hypertrophy during resistance training in young adults. J Appl Physiol (1985) 2023; 134:753-765. [PMID: 36794689 DOI: 10.1152/japplphysiol.00698.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/17/2023] Open
Abstract
We have previously shown that maximal over-the-counter doses of ibuprofen, compared with low doses of acetylsalicylic acid, reduce muscle hypertrophy in young individuals after 8 wk of resistance training. Because the mechanism behind this effect has not been fully elucidated, we here investigated skeletal muscle molecular responses and myofiber adaptations in response to acute and chronic resistance training with concomitant drug intake. Thirty-one young (aged 18-35 yr) healthy men (n = 17) and women (n = 14) were randomized to receive either ibuprofen (IBU; 1,200 mg daily; n = 15) or acetylsalicylic acid (ASA; 75 mg daily; n = 16) while undergoing 8 wk of knee extension training. Muscle biopsies from the vastus lateralis were obtained before, at week 4 after an acute exercise session, and after 8 wk of resistance training and analyzed for mRNA markers and mTOR signaling, as well as quantification of total RNA content (marker of ribosome biogenesis) and immunohistochemical analysis of muscle fiber size, satellite cell content, myonuclear accretion, and capillarization. There were only two treatment × time interaction in selected molecular markers after acute exercise (atrogin-1 and MuRF1 mRNA), but several exercise effects. Muscle fiber size, satellite cell and myonuclear accretion, and capillarization were not affected by chronic training or drug intake. RNA content increased comparably (∼14%) in both groups. Collectively, these data suggest that established acute and chronic hypertrophy regulators (including mTOR signaling, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis) were not differentially affected between groups and therefore do not explain the deleterious effects of ibuprofen on muscle hypertrophy in young adults.NEW & NOTEWORTHY Here we show that mTOR signaling, fiber size, ribosome biogenesis, satellite cell content, myonuclear accretion, and angiogenesis were not differentially affected between groups undergoing 8 wk of resistance training with concomitant anti-inflammatory medication (ibuprofen versus low-dose aspirin). Atrogin-1 and MuRF-1 mRNA were more downregulated after acute exercise in the low-dose aspirin group than in the ibuprofen group. Taken together it appears that these established hypertrophy regulators do not explain the previously reported deleterious effects of high doses of ibuprofen on muscle hypertrophy in young adults.
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Affiliation(s)
- Mats Lilja
- Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
| | - Marcus Moberg
- Department of Physiology, Nutrition and Biomechanics, Swedish School of Sport and Health Sciences, Stockholm, Sweden
| | - William Apró
- Department of Physiology, Nutrition and Biomechanics, Swedish School of Sport and Health Sciences, Stockholm, Sweden
| | - Luis Manuel Martínez-Aranda
- Movement Analysis Laboratory for Sport and Health (MALab), Faculty of Sport, Catholic University of Murcia, Murcia, Spain
| | - Håkan Rundqvist
- Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
| | - Billy Langlet
- Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden
| | - Thomas Gustafsson
- Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
| | - Tommy R Lundberg
- Division of Clinical Physiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.,Unit of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden
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Hamasaki H. High-intensity Interval Training in Patients with Type 2 Diabetes: A Perspective from Previous Systematic Reviews. Endocr Metab Immune Disord Drug Targets 2023; 23:1248-1253. [PMID: 37005528 DOI: 10.2174/1871530323666230330124105] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 02/11/2023] [Accepted: 02/16/2023] [Indexed: 04/04/2023]
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Kindlovits R, Pereira AMDS, Sousa AC, Viana JL, Teixeira VH. Effects of Acute and Chronic Exercise in Hypoxia on Cardiovascular and Glycemic Parameters in Patients with Type 2 Diabetes: A Systematic Review. High Alt Med Biol 2022; 23:301-312. [PMID: 36036723 DOI: 10.1089/ham.2022.0029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023] Open
Abstract
Kindlovits, Raquel, Alberto Mello da Silva Pereira, Ana Catarina Sousa, João Luís Viana,and Vitor Hugo Teixeira. Effects of acute and chronic exercise in hypoxia on cardiovascular and glycemic parameters in patients with type 2 diabetes: a systematic review. High Alt Med Biol. 23:301-312, 2022. Background: Exercise in hypoxia (EH, decreased oxygen availability) has been proposed as a potential therapeutic intervention to promote angiogenesis and improve glucose metabolism to a greater extent than exercise under normoxia (normal ambient air) in patients with type 2 diabetes (T2D). Currently, there are no studies that systematize the existent evidence. This study aims to systematically review the literature and qualitatively evaluate the effects of acute and chronic EH on cardiovascular and glycemic parameters in T2D patients. Methods: A structured search was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines until March 2021, in the MEDLINE/PubMed, Scopus, and Web of Science databases. The inclusion criteria were as follows: (1) randomized and nonrandomized trials, (2) in complication-free patients with T2D, (3) in which EH was compared with exercise in normoxia or with baseline data, and (4) published in English. Results: Six articles (64 subjects) met the inclusion criteria and were reviewed to data extraction. Four articles investigated the acute effect of EH (33 subjects), and two articles investigated the chronic effect of EH (31 subjects), ranging from 6 to 8 weeks. All studies used a cycle ergometer as exercise. Acute EH benefits insulin sensitivity, blood glucose, vascular endothelial growth factor, and metalloproteinase-9, while chronic EH benefits nitric oxide synthase in erythrocytes, but not brachial artery flow-mediated dilation. Conclusion: Acute EH improves glucose homeostasis in T2D patients, which was not seen with chronic EH. Both acute EH and chronic EH improve angiogenesis regulators, but not vascular function. Despite the putative benefits of EH in patients with T2D, the evidence is still scarce and further research is needed before recommendations can be provided.
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Affiliation(s)
- Raquel Kindlovits
- Faculty of Nutrition and Food Sciences, University of Porto (FCNAUP), Porto, Portugal
| | | | - Ana Catarina Sousa
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, Maia, Portugal
| | - João Luís Viana
- Research Center in Sports Sciences, Health Sciences and Human Development (CIDESD), University of Maia, Maia, Portugal
| | - Vitor Hugo Teixeira
- Faculty of Nutrition and Food Sciences, University of Porto (FCNAUP), Porto, Portugal.,Research Center in Physical Activity, Health and Leisure (CIAFEL), Faculty of Sports, University of Porto (FADEUP), Portugal.,Laboratory for Integrative and Translational Research in Population Health (ITR), Porto, Portugal
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Gül N, Cebesoy S, Özsoy N, Eskizengin H, Özer Ç. The Ultrastructure of Skeletal Muscle Capillaries of Streptozotocin Diabetic Rats and the Therapeutic Effect of Benfluorex. MICROSCOPY AND MICROANALYSIS : THE OFFICIAL JOURNAL OF MICROSCOPY SOCIETY OF AMERICA, MICROBEAM ANALYSIS SOCIETY, MICROSCOPICAL SOCIETY OF CANADA 2022; 28:1-5. [PMID: 36205173 DOI: 10.1017/s143192762201251x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Diabetes mellitus is a serious disease worldwide and causes other associated diseases. In this study, we observed the effect of streptozotocin (STZ)-induced diabetes and benfluorex treatment on muscular capillary ultrastructure. Adult male rats were used as the test subjects and each individual was intraperitoneally injected with one dose of STZ (45 mg/kg) to induce diabetes. Doses (50 mg/kg) of benfluorex were given to the subjects with tap water by intragastric gavage application once daily for 21 days. At the end of day 21, muscle tissues were obtained from animals and examined under transmission electron microscopy. From the data obtained with the electron microscope, it was observed that the control group had typical continuous capillary vascular structures in their muscles, while STZ caused disruptive disorder of the muscle cells in the capillary wall of the STZ-diabetic group. Additionally, the thickening of the basement membrane around endothelial cells, loss of mitochondrial crista in the muscle cells, enlarged endothelial cells, and narrowed vessel lumen were observed in the muscle tissue. The findings of our study revealed that STZ-induced diabetes disrupted the vascular structure, while benfluorex partially improved it.
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Affiliation(s)
- Nursel Gül
- Faculty of Sciences, Biology Department, Ankara University, Tandogan, Ankara 06100, Turkey
| | - Suna Cebesoy
- Faculty of Sciences, Biology Department, Ankara University, Tandogan, Ankara 06100, Turkey
| | - Nesrin Özsoy
- Faculty of Sciences, Biology Department, Ankara University, Tandogan, Ankara 06100, Turkey
| | - Hakan Eskizengin
- Faculty of Sciences, Biology Department, Ankara University, Tandogan, Ankara 06100, Turkey
| | - Çiğdem Özer
- School of Medicine, Physiology Department, Gazi University, Besevler, Ankara 06500, Turkey
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YANG MINGXUAN, PAN YANXIA, LI KUNHUI, CHEN XIUYUN, LI MINYAN, LIN JIANPING, LI MING, LIN CHENG. Effects of Exercise Training on PPARβ/δ Expression in Skeletal Muscle of Rats with Spontaneous Hypertension. Med Sci Sports Exerc 2022; 54:1309-1316. [PMID: 35389955 PMCID: PMC9301982 DOI: 10.1249/mss.0000000000002925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
PURPOSE This study aimed to identify the relationship and mechanism between skeletal muscle peroxisome proliferator-activated receptor β/δ (PPARβ/δ) and spontaneous hypertension. METHODS Rats were divided into four groups ( n = 10): spontaneous hypertensive rats exercise group (SHR-E), spontaneous hypertensive rats sedentary group (SHR-S), Wistar-Kyoto control rats exercise group (WKY-E), and Wistar-Kyoto control rats sedentary group (WKY-S). Although the sedentary groups were placed on the treadmill without moving during the training sessions, the exercise groups were forced to run on a treadmill for 8 wk, 1 h·d -1 , 5 d·wk -1 . After training, the density and area of gastrocnemius microvessels were observed. PPARβ/δ, vascular endothelial growth factor A (VEGFA), superoxide dismutase 2 (SOD-2), and nitric oxide synthase in gastrocnemius were measured by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot. RESULTS Except the sixth week of age, the systolic blood pressure of SHR-S was significantly higher than that of WKY-S at all time periods. Exercise significantly reduced systolic blood pressure in SHR rats. Compared with the SHR-S group, the WKY-S group had significantly higher PPARβ/δ protein level and density of skeletal muscle microvessels. Eight weeks of exercise increased the PPARβ/δ, SOD-2, VEGFA, and microvessel density and area in the skeletal muscle of SHR. CONCLUSIONS Exercise training promoted PPARβ/δ mRNA and protein-level expression of PPARβ/δ, SOD-2 and VEGFA in skeletal muscle, thus increasing the density and area of skeletal muscle blood vessels. These regulations contribute to the reduction of peripheral vascular resistance. This may be a potential mechanism of exercise to reduce blood pressure.
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Affiliation(s)
- MINGXUAN YANG
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
- Department of Rehabilitation Medicine, The Second Affiliated Hospital of Kunming Medical University, Kunming, CHINA
| | - YANXIA PAN
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - KUNHUI LI
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - XIUYUN CHEN
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - MINYAN LI
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - JIANPING LIN
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - MING LI
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
| | - CHENG LIN
- Department of Rehabilitation Therapy, School of Health, Fujian Medical University, Fuzhou, CHINA
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Mateo-Gallego R, Madinaveitia-Nisarre L, Giné-Gonzalez J, María Bea A, Guerra-Torrecilla L, Baila-Rueda L, Perez-Calahorra S, Civeira F, Lamiquiz-Moneo I. The effects of high-intensity interval training on glucose metabolism, cardiorespiratory fitness and weight control in subjects with diabetes: Systematic review a meta-analysis. Diabetes Res Clin Pract 2022; 190:109979. [PMID: 35780905 DOI: 10.1016/j.diabres.2022.109979] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Accepted: 06/27/2022] [Indexed: 11/27/2022]
Abstract
AIM The objective of this meta-analysis was to explore the effects of high-intensity interval training (HIIT) compared with control conditions (CON) or moderate intensity continuous training (MICT) on glycemic parameters in diabetes subjects. METHODS Pubmed, Embase and Google Scholar databases were searched for HIIT interventions that were carried out in diabetic subjects and exploring fasting glucose, glycated haemoglobin (HbA1c), fasting insulin and/or HOMA-IR. RESULTS This systematic review retrieved a total of 1741 studies of which 32 articles fulfilled the eligibility criteria. Nineteen trials were included in the meta-analysis since they compared HIIT intervention with CON or MICT group. There was a significantly reduction of fasting glucose of 13.3 mg/dL (p < 0.001), Hb1Ac -0.34% (p < 0.001), insulin -2.27 UI/L (p = 0.003), HOMA-IR -0.88 (p = 0.005) in the HIIT-group compared with CON-group. Nevertheless, this reduction was not significantly different when comparing HIIT with MICT (p = 0.140, p = 0.315, p = 0.520 and p = 0.389). Besides, there was a significant increase of absolute VO2max of 0.21 L/min (p < 0.001) and relative VO2max of 2.94 ml/kg/min (p < 0.001) in the HIIT-group compared with the CON-group and the MICT-group (0.22 L/min, p = 0.025) and (0.97 ml/kg/min, p = 0.045). CONCLUSIONS These findings revealed that HIIT intervention led to significant improvement in glycemic control and insulin resistance in subjects with diabetes compared with CON-group.
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Affiliation(s)
- Rocío Mateo-Gallego
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain; Department of Physiatry and Nursing. Facultad de Ciencias de la Salud y del Deporte, Universidad de Za-ragoza, 22002 Huesca, Spain
| | - Loreto Madinaveitia-Nisarre
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain
| | - Jaume Giné-Gonzalez
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain
| | - Ana María Bea
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain
| | - Lydia Guerra-Torrecilla
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain
| | - Lucía Baila-Rueda
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain
| | - Sofia Perez-Calahorra
- Department of Physiatry and Nursing. Facultad de Ciencias de la Salud y del Deporte, Universidad de Za-ragoza, 22002 Huesca, Spain
| | - Fernando Civeira
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain; Department of Medicine, Psychiatry and Dermatology. Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain
| | - Itziar Lamiquiz-Moneo
- Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria Aragón (IIS Aragón), CIBERCV, Universidad de Zaragoza, Zaragoza, Spain; Department of Human Anatomy and Histology. Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain.
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Hulett NA, Scalzo RL, Reusch JEB. Glucose Uptake by Skeletal Muscle within the Contexts of Type 2 Diabetes and Exercise: An Integrated Approach. Nutrients 2022; 14:647. [PMID: 35277006 PMCID: PMC8839578 DOI: 10.3390/nu14030647] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 01/25/2022] [Accepted: 01/28/2022] [Indexed: 02/01/2023] Open
Abstract
Type 2 diabetes continues to negatively impact the health of millions. The inability to respond to insulin to clear blood glucose (insulin resistance) is a key pathogenic driver of the disease. Skeletal muscle is the primary tissue for maintaining glucose homeostasis through glucose uptake via insulin-dependent and -independent mechanisms. Skeletal muscle is also responsive to exercise-meditated glucose transport, and as such, exercise is a cornerstone for glucose management in people with type 2 diabetes. Skeletal muscle glucose uptake requires a concert of events. First, the glucose-rich blood must be transported to the skeletal muscle. Next, the glucose must traverse the endothelium, extracellular matrix, and skeletal muscle membrane. Lastly, intracellular metabolic processes must be activated to maintain the diffusion gradient to facilitate glucose transport into the cell. This review aims to examine the physiology at each of these steps in healthy individuals, analyze the dysregulation affecting these pathways associated with type 2 diabetes, and describe the mechanisms by which exercise acts to increase glucose uptake.
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Affiliation(s)
- Nicholas A. Hulett
- Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA; (N.A.H.); (R.L.S.)
| | - Rebecca L. Scalzo
- Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA; (N.A.H.); (R.L.S.)
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO 80045, USA
- Center for Women’s Health Research, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
| | - Jane E. B. Reusch
- Department of Medicine, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA; (N.A.H.); (R.L.S.)
- Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO 80045, USA
- Center for Women’s Health Research, Anschutz Medical Campus, University of Colorado, Aurora, CO 80045, USA
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de Mello MB, Righi NC, Schuch FB, Signori LU, da Silva AMV. Effect of high-intensity interval training protocols on VO 2max and HbA1c level in people with type 2 diabetes: A systematic review and meta-analysis. Ann Phys Rehabil Med 2021; 65:101586. [PMID: 34648979 DOI: 10.1016/j.rehab.2021.101586] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 07/19/2021] [Accepted: 08/10/2021] [Indexed: 12/16/2022]
Abstract
BACKGROUND The effect of high-intensity interval training (HIIT) protocols according to different work intervals, session volumes and training periods has not been evaluated in patients with type 2 diabetes mellitus (T2DM). OBJECTIVE This was a systematic review and meta-analysis of the effect of HIIT and its different protocols compared to moderate-intensity continuous training (MICT) and the control group on VO2max and glycated hemoglobin (HbA1c) level in patients with T2DM. METHODS The search strategy considered studies published up to September 2020 in the databases MEDLINE (PubMed), EMBASE, Cochrane CENTRAL, Web of Science and SPORTDiscus. Two authors independently searched the selected databases for randomized clinical trials that compared HIIT to MICT or the control in adults with T2DM. A random-effects meta-analysis was performed and the data are presented as the mean difference (95% confidence intervals [95% CIs]) between HIIT, MICT and control groups. RESULTS A total of 20 studies (738 participants) were included. Overall, HIIT increased VO2max by 5.09 mL/kg/min (95% CI 2.99; 7.19, I² = 80.89) versus the control and by 1.9 mL/kg/min (95% CI 0.81; 2.98, I² = 25.62) versus MICT. HIIT promoted a significant reduction in HbA1c level of -0.8% (95% CI -1.06; -0.49, I² = 77.31) versus the control but with no difference versus MICT. Moderate-interval, high-volume and long-term training promoted a greater increase in VO2max. A long interval and moderate volume and period conferred a greater increase in VO2max versus MICT. A short interval and moderate volume and period conferred a greater reduction in HbA1c level versus the control. No publication bias was detected, as evaluated by a funnel chart and Egger's test (p > 0.05). CONCLUSIONS As compared with MICT, HIIT had better effect on VO2max and a similar effect on HbA1C level. Interval protocols, moderate to long training period and moderate to high volume may maximize the HIIT effect in patients with T2DM.
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Affiliation(s)
- Mariana Brondani de Mello
- Postgraduate Program in Functional Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Natiele Camponogara Righi
- Postgraduate Program in Rehabilitation Sciences at the Federal University of Health Sciences of Porto Alegre, Porto Alegre, Brazil
| | - Felipe Barreto Schuch
- Department of Sports Methods and Techniques, Federal University of Santa Maria, Santa Maria, Brazil; Department of Physiotherapy and Rehabilitation, Post-Graduate Programme in Functional Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Luis Ulisses Signori
- Department of Physiotherapy and Rehabilitation, Post-Graduate Programme in Functional Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil
| | - Antônio Marcos Vargas da Silva
- Department of Physiotherapy and Rehabilitation, Post-Graduate Programme in Functional Rehabilitation, Federal University of Santa Maria, Santa Maria, Brazil.
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Jaconiano E, Moreira-Gonçalves D. Unveiling the role of exercise training in targeting the inflammatory paradigm of heart failure with preserved ejection fraction: a narrative review. Heart Fail Rev 2021; 27:163-190. [PMID: 34244870 DOI: 10.1007/s10741-021-10138-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/01/2021] [Indexed: 12/30/2022]
Abstract
Heart failure with preserved ejection fraction (HFpEF) is currently lacking an effective pharmacological treatment with impact on major outcomes such as hospitalization and mortality. Exercise training (EXT) is recognized as an important nonpharmacological tool, capable of improving exercise capacity and quality of life, and has even been associated with a reduction in hospitalization and cardiovascular mortality risk. However, this positive impact largely lacks a physiological explanation. The aim of this narrative review was to provide an overview of the available data supporting the hypothesis that the beneficial role of EXT in HFpEF might be due to its effects on targeting the inflammatory paradigm described for this disease. A comprehensive literature search was conducted using the PubMed-NCBI database. We reviewed the effects of EXT throughout each step of the pathophysiological pathway leading to HFpEF and found clinical and/or preclinical evidence supporting the reduction of systemic inflammation, endothelial dysfunction, microvascular rarefaction, and myocardial stiffness. We also highlighted some gaps in the knowledge or topics that deserve further clarification in future studies. In conclusion, despite the scarcity of clinical studies in this population, there is compelling evidence suggesting that EXT modulates crucial aspects of the inflammatory pathway described for HFpEF and future investigation on cellular and molecular mechanisms are encouraged.
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Affiliation(s)
- Eliane Jaconiano
- Cardiovascular R&D Center (UnIC) and Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, Porto, Portugal.
| | - Daniel Moreira-Gonçalves
- Centre of Physical Activity, Health and Leisure (CIAFEL), Faculty of Sport, University of Porto, Porto, Portugal
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An Extended Approach to Predict Retinopathy in Diabetic Patients Using the Genetic Algorithm and Fuzzy C-Means. BIOMED RESEARCH INTERNATIONAL 2021; 2021:5597222. [PMID: 34258269 PMCID: PMC8257333 DOI: 10.1155/2021/5597222] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 06/19/2021] [Indexed: 01/23/2023]
Abstract
The present study is developed a new approach using a computer diagnostic method to diagnosing diabetic diseases with the use of fluorescein images. In doing so, this study presented the growth region algorithm for the aim of diagnosing diabetes, considering the angiography images of the patients' eyes. In addition, this study integrated two methods, including fuzzy C-means (FCM) and genetic algorithm (GA) to predict the retinopathy in diabetic patients from angiography images. The developed algorithm was applied to a total of 224 images of patients' retinopathy eyes. As clearly confirmed by the obtained results, the GA-FCM method outperformed the hand method regarding the selection of initial points. The proposed method showed 0.78 sensitivity. The comparison of the fuzzy fitness function in GA with other techniques revealed that the approach introduced in this study is more applicable to the Jaccard index since it could offer the lowest Jaccard distance and, at the same time, the highest Jaccard values. The results of the analysis demonstrated that the proposed method was efficient and effective to predict the retinopathy in diabetic patients from angiography images.
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Paquin J, Lagacé JC, Brochu M, Dionne IJ. Exercising for Insulin Sensitivity - Is There a Mechanistic Relationship With Quantitative Changes in Skeletal Muscle Mass? Front Physiol 2021; 12:656909. [PMID: 34054574 PMCID: PMC8149906 DOI: 10.3389/fphys.2021.656909] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 04/14/2021] [Indexed: 12/29/2022] Open
Abstract
Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.
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Affiliation(s)
- Jasmine Paquin
- Research Centre on Aging, Affiliated With CIUSSS de l'Estrie-CHUS, Sherbrooke, QC, Canada.,Faculty of Physical Activity Sciences, University of Sherbrooke, Sherbrooke, QC, Canada
| | - Jean-Christophe Lagacé
- Research Centre on Aging, Affiliated With CIUSSS de l'Estrie-CHUS, Sherbrooke, QC, Canada.,Faculty of Physical Activity Sciences, University of Sherbrooke, Sherbrooke, QC, Canada
| | - Martin Brochu
- Research Centre on Aging, Affiliated With CIUSSS de l'Estrie-CHUS, Sherbrooke, QC, Canada.,Faculty of Physical Activity Sciences, University of Sherbrooke, Sherbrooke, QC, Canada
| | - Isabelle J Dionne
- Research Centre on Aging, Affiliated With CIUSSS de l'Estrie-CHUS, Sherbrooke, QC, Canada.,Faculty of Physical Activity Sciences, University of Sherbrooke, Sherbrooke, QC, Canada
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Gildea N, McDermott A, Rocha J, O’Shea D, Green S, Egaña M. Time course of changes in V̇o2peak and O2 extraction during ramp cycle exercise following HIIT versus moderate-intensity continuous training in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 2021; 320:R683-R696. [DOI: 10.1152/ajpregu.00318.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
In the present study, we assessed the time course of adaptations in peak oxygen uptake (V̇o2peak) and muscle fractional oxygen (O2) extraction (using near-infrared spectroscopy) following 12 wk of low-volume high-intensity interval training (HIIT) versus moderate-intensity continuous endurance training (MICT) in adults with uncomplicated type 2 diabetes (T2D). Participants with T2D were randomly assigned to MICT ( n = 12, 50 min of moderate-intensity cycling) or HIIT ( n = 9, 10 × 1 min at ∼90% maximal heart rate) or to a nonexercising control group ( n = 9). Exercising groups trained three times per week and measurements were taken every 3 wk. The rate of muscle deoxygenation (i.e., deoxygenated hemoglobin and myoglobin concentration, Δ[HHb + Mb]) profiles of the vastus lateralis muscle were normalized to 100% of the response, plotted against % power output (PO), and fitted with a double linear regression model. V̇o2peak increased ( P < 0.05) by week 3 of MICT (+17%) and HIIT (+8%), with no further significant changes thereafter. Total increases in V̇o2peak posttraining ( P < 0.05) were 27% and 14%, respectively. The %Δ[HHb + Mb] versus %PO slope of the first linear segment ( slope1) was reduced ( P < 0.05) beyond 3 wk of HIIT and MICT, with no further significant changes thereafter. No changes in V̇o2peak or slope1 were observed in the control group. Low-volume HIIT and MICT induced improvements in V̇o2peak following a similar time course, and these improvements were likely, at least in part, due to an improved microvascular O2 delivery.
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Affiliation(s)
- Norita Gildea
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Adam McDermott
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Joel Rocha
- Division of Sport and Exercise Sciences, Abertay University, Dundee, United Kingdom
| | - Donal O’Shea
- Department of Endocrinology, St. Columcille’s Hospital, Dublin, Ireland
- Department of Endocrinology and Diabetes Mellitus, St. Vincent’s University Hospital, Dublin, Ireland
| | - Simon Green
- Schools of Health Sciences and Medicine, Western Sydney University, Sydney, Australia
| | - Mikel Egaña
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
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Gildea N, McDermott A, Rocha J, O'Shea D, Green S, Egaña M. Time-course of V̇o 2 kinetics responses during moderate-intensity exercise subsequent to HIIT versus moderate-intensity continuous training in type 2 diabetes. J Appl Physiol (1985) 2021; 130:1646-1659. [PMID: 33792400 DOI: 10.1152/japplphysiol.00952.2020] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
We assessed the time-course of changes in oxygen uptake (V̇o2) and muscle deoxygenation (i.e., deoxygenated hemoglobin and myoglobin, [HHb + Mb]) kinetics during transitions to moderate-intensity cycling following 12 wk of low-volume high-intensity interval training (HIIT) vs. moderate-intensity continuous training (MICT) in adults with type 2 diabetes (T2D). Participants were randomly assigned to MICT (n = 10, 50 min of moderate-intensity cycling), HIIT (n = 9, 10 × 1 min at ∼90% maximal heart rate), or nonexercising control (n = 9) groups. Exercising groups trained three times per week, and measurements were taken every 3 wk. [HHb + Mb] kinetics were measured by near-infrared spectroscopy at the vastus lateralis muscle. The local matching of O2 delivery to O2 utilization was assessed by the Δ[HHb + Mb]/ΔV̇o2 ratio. The pretraining time constant of the primary phase of V̇o2 (τV̇o2p) decreased (P < 0.05) at wk 3 of training in both MICT (from 44 ± 12 to 32 ± 5 s) and HIIT (from 42 ± 8 to 32 ± 4 s) with no further changes thereafter, whereas no changes were reported in controls. The pretraining overall dynamic response of muscle deoxygenation (τ'[HHb + Mb]) was faster than τV̇o2p in all groups, resulting in Δ[HHb + Mb]/V̇o2p showing a transient "overshoot" relative to the subsequent steady-state level. After 3 wk, the Δ[HHb + Mb]/V̇o2p overshoot was eliminated only in the training groups, so that τ'[HHb + Mb] was not different to τV̇o2p in MICT and HIIT. The enhanced V̇o2 kinetics response consequent to both MICT and HIIT in T2D was likely attributed to a training-induced improvement in matching of O2 delivery to utilization.NEW & NOTEWORTHY High-intensity interval training and moderate-intensity continuous training elicited faster pulmonary oxygen uptake (V̇o2) kinetics during moderate-intensity cycling within 3 wk of training with no further changes thereafter in individuals with type 2 diabetes. These adaptations were accompanied by unaltered near-infrared spectroscopy-derived muscle deoxygenation (i.e. deoxygenated hemoglobin and myoglobin concentration, [HHb+Mb]) kinetics and transiently reduced Δ[HHb+Mb]-to-ΔV̇o2 ratio, suggesting an enhanced blood flow distribution within the active muscles subsequent to both training interventions.
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Affiliation(s)
- Norita Gildea
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Adam McDermott
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
| | - Joel Rocha
- Division of Sport and Exercise Sciences, Abertay University, Dundee, United Kingdom
| | - Donal O'Shea
- Department of Endocrinology, St. Columcille's Hospital, Dublin, Ireland.,Department of Endocrinology and Diabetes Mellitus, St. Vincent's University Hospital, Dublin, Ireland
| | - Simon Green
- Schools of Health Sciences and Medicine, Western Sydney University, Sydney, Australia
| | - Mikel Egaña
- Department of Physiology, School of Medicine, Trinity College Dublin, Dublin, Ireland
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Lam B, Nwadozi E, Haas TL, Birot O, Roudier E. High Glucose Treatment Limits Drosha Protein Expression and Alters AngiomiR Maturation in Microvascular Primary Endothelial Cells via an Mdm2-dependent Mechanism. Cells 2021; 10:742. [PMID: 33801773 PMCID: PMC8065922 DOI: 10.3390/cells10040742] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2021] [Revised: 03/20/2021] [Accepted: 03/23/2021] [Indexed: 12/21/2022] Open
Abstract
Diabetes promotes an angiostatic phenotype in the microvascular endothelium of skeletal muscle and skin. Angiogenesis-related microRNAs (angiomiRs) regulate angiogenesis through the translational repression of pro- and anti-angiogenic genes. The maturation of micro-RNA (miRs), including angiomiRs, requires the action of DROSHA and DICER proteins. While hyperglycemia modifies the expression of angiomiRs, it is unknown whether high glucose conditions alter the maturation process of angiomiRs in dermal and skeletal muscle microvascular endothelial cells (MECs). Compared to 5 mM of glucose, high glucose condition (30 mM, 6-24 h) decreased DROSHA protein expression, without changing DROSHA mRNA, DICER mRNA, or DICER protein in primary dermal MECs. Despite DROSHA decreasing, high glucose enhanced the maturation and expression of one angiomiR, miR-15a, and downregulated an miR-15a target: Vascular Endothelial Growth Factor-A (VEGF-A). The high glucose condition increased Murine Double Minute-2 (MDM2) expression and MDM2-binding to DROSHA. Inhibition of MDM2 prevented the effects evoked by high glucose on DROSHA protein and miR-15a maturation in dermal MECs. In db/db mice, blood glucose was negatively correlated with the expression of skeletal muscle DROSHA protein, and high glucose decreased DROSHA protein in skeletal muscle MECs. Altogether, our results suggest that high glucose reduces DROSHA protein and enhances the maturation of the angiostatic miR-15a through a mechanism that requires MDM2 activity.
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Zinn S, Nelis P, Minnebeck K, Hinder J, Eter N, Brand SM, Gellner R, Vorona E, Alten F, Schmitz B. Effect of high-intensity interval training in patients with type 1 diabetes on physical fitness and retinal microvascular perfusion determined by optical coherence tomography angiography. Microvasc Res 2020; 132:104057. [DOI: 10.1016/j.mvr.2020.104057] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2020] [Revised: 08/03/2020] [Accepted: 08/08/2020] [Indexed: 12/01/2022]
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Dantas WS, Roschel H, Murai IH, Gil S, Davuluri G, Axelrod CL, Ghosh S, Newman SS, Zhang H, Shinjo SK, das Neves W, Merege-Filho C, Teodoro WR, Capelozzi VL, Pereira RM, Benatti FB, de Sá-Pinto AL, de Cleva R, Santo MA, Kirwan JP, Gualano B. Exercise-Induced Increases in Insulin Sensitivity After Bariatric Surgery Are Mediated By Muscle Extracellular Matrix Remodeling. Diabetes 2020; 69:1675-1691. [PMID: 32409493 PMCID: PMC7372074 DOI: 10.2337/db19-1180] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 05/08/2020] [Indexed: 02/06/2023]
Abstract
Exercise seems to enhance the beneficial effect of bariatric (Roux-en-Y gastric bypass [RYGB]) surgery on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underlie these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB (RYGB + ET) or standard of care (RYGB). Insulin sensitivity was assessed by oral glucose tolerance test. Muscle biopsy specimens were obtained at baseline and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification, and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index: RYGB 123% vs. RYGB + ET 325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I: RYGB -41% vs. RYGB + ET -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-β1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle ECM remodeling.
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Affiliation(s)
- Wagner S Dantas
- Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Hamilton Roschel
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Igor H Murai
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Saulo Gil
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Gangarao Davuluri
- Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Christopher L Axelrod
- Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
- Department of Translational Services, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Sujoy Ghosh
- Genomics Core, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
- Cardiovascular and Metabolic Disorders Program and Center for Computational Biology, Duke-National University of Singapore Medical School, Singapore
| | - Susan S Newman
- Genomics Core, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Hui Zhang
- Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Samuel K Shinjo
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Willian das Neves
- Clinical Oncology Service, Instituto do Câncer do Estado de São Paulo, São Paulo, Brazil
| | - Carlos Merege-Filho
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Walcy R Teodoro
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Vera L Capelozzi
- Department of Pathology, School of Medicine, Universidade de São Paulo, São Paulo, Brazil
| | - Rosa Maria Pereira
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Fabiana B Benatti
- School of Applied Sciences, Universidade Estadual de Campinas, São Paulo, Brazil
| | - Ana L de Sá-Pinto
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
| | - Roberto de Cleva
- Department of Digestive Division, School of Medicine, Universidade de São Paulo, São Paulo, Brazil
| | - Marco A Santo
- Department of Digestive Division, School of Medicine, Universidade de São Paulo, São Paulo, Brazil
| | - John P Kirwan
- Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA
| | - Bruno Gualano
- Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
- Rheumatology Division, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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Parise G, Murrant CL, Cocks M, Snijders T, Baum O, Plyley MJ. Capillary facilitation of skeletal muscle function in health and disease. Appl Physiol Nutr Metab 2020; 45:453-462. [DOI: 10.1139/apnm-2019-0416] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Skeletal muscle is highly vascularized, with perfusion being tightly regulated to meet wide-ranging metabolic demands. For decades, the capillary supply has been explored mainly in terms of evaluating the capillary numbers and their function in the supply of oxygen and substrates and the removal of metabolic byproducts. This review will focus on recent discoveries concerning the role played by capillaries in facilitating other aspects of cell regulation and maintenance, in health and disease, as well as alterations during the aging process. Novelty Capillaries play a central role in the coordination of the vascular response that controls blood flow during contraction and the cellular responses to which they feed into. Nitric oxide is an important regulatory compound within the cardiovascular system, and a significant contributor to skeletal muscle capillary angiogenesis and vasodilatory response to agonists. The microvascular network between muscle fibres may play a critical role in the distribution of signalling factors necessary for optimal muscle satellite cell function.
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Affiliation(s)
- Gianni Parise
- McMaster University, Departments of Kinesiology and Medical Physics & Applied Radiation Science, Hamilton, ON L8S 4K1, Canada
| | - Coral L. Murrant
- Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, N1G 2W1, Canada
| | - Matthew Cocks
- Liverpool John Moores University, Research Institute for Sport and Exercise Sciences, Liverpool, L3 5UG, UK
| | - Tim Snijders
- Maastricht University, NUTRIM School of Nutrition and Translational Research in Metabolism, Department of Human Biology, Maastricht 6200 MD, the Netherlands
| | - Oliver Baum
- Institute of Physiology, Charité-Universitäts medizin Berlin, Berlin D-10117, Germany
| | - Michael J. Plyley
- Brock University, Department of Kinesiology, St. Catharines, ON L2S 3A1, Canada
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Baum O, Bernd J, Becker S, Odriozola A, Zuber B, Tschanz SA, Zakrzewicz A, Egginton S, Berkholz J. Structural Microangiopathies in Skeletal Muscle Related to Systemic Vascular Pathologies in Humans. Front Physiol 2020; 11:28. [PMID: 32116748 PMCID: PMC7013089 DOI: 10.3389/fphys.2020.00028] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 01/15/2020] [Indexed: 12/17/2022] Open
Abstract
It is unclear how microangiopathic changes in skeletal muscle vary among systemic vascular pathologies. We therefore analyzed the capillary fine structure in skeletal muscle from patients with arterial hypertension (HYPT), diabetes mellitus type 2 (T2DM) or intermittent claudication – peripheral arterial disease (IC/PAD). Tablet-based image analysis (TBIA) was carried out to largely re-evaluate 5,000 transmission electron micrographs of capillaries from 126 vastus lateralis biopsies of 75 individuals (HYPT, T2DM or IC/PAD patients as well as healthy individuals before and after endurance exercise training) used in previous morphometric studies, but assessed using stereological counting grids of different sizes. Serial block-face scanning electron microscopy (SBFSEM) of mouse skeletal muscle was used for validation of the particular fine structural events observed in human biopsies. The peri-capillary basement membrane (BM) was 38.5 and 45.5% thicker (P < 0.05) in T2DM and IC/PAD patients than in the other groups. A 17.7–39.6% lower (P < 0.05) index for intraluminal endothelial cell (EC) surface enlargement by projections was exclusively found in T2DM patients by TBIA morphometry. The proportion of capillaries with disrupted BM between pericytes (PC) and EC was higher (P < 0.05) in HYPT (33.2%) and T2DM (38.7%) patients than in the control group. Empty EC-sockets were more frequent (P < 0.05) in the three patient groups (20.6% in HYPT, 27.1% in T2DM, 30.0% in IC/PAD) than in the healthy individuals. SBFSEM confirmed that EC-sockets may exhibit close proximity to the capillary lumen. Our comparative morphometric analysis demonstrated that structural arrangement of skeletal muscle capillaries is more affected in T2DM than in HYPT or IC/PAD, although some similar elements of remodeling were found. The increased frequency of empty EC-sockets in the three patient groups indicates that the PC-EC interaction is commonly disturbed in these systemic vascular pathologies.
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Affiliation(s)
- Oliver Baum
- Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Jonathan Bernd
- Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Samuel Becker
- Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | | | - Benoît Zuber
- Institute of Anatomy, University of Bern, Bern, Switzerland
| | | | - Andreas Zakrzewicz
- Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
| | - Stuart Egginton
- School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom
| | - Janine Berkholz
- Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin, Germany
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Angleys H, Østergaard L. Krogh’s capillary recruitment hypothesis, 100 years on: Is the opening of previously closed capillaries necessary to ensure muscle oxygenation during exercise? Am J Physiol Heart Circ Physiol 2020; 318:H425-H447. [DOI: 10.1152/ajpheart.00384.2019] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
In 1919, August Krogh published his seminal work on skeletal muscle oxygenation. Krogh’s observations indicated that muscle capillary diameter is actively regulated, rather than a passive result of arterial blood flow regulation. Indeed, combining a mathematical model with the number of ink-filled capillaries he observed in muscle cross sections taken at different workloads, Krogh was able to account for muscle tissue’s remarkably efficient oxygen extraction during exercise in terms of passive diffusion from nearby capillaries. Krogh was awarded the 1920 Nobel Prize for his account of muscle oxygenation. Today, his observations are engrained in the notion of capillary recruitment: the opening of previously closed capillaries. While the binary distinction between “closed” and “open” was key to Krogh’s model argument, he did in fact report a continuum of capillary diameters, degrees of erythrocyte deformation, and perfusion states. Indeed, modern observations question the presence of closed muscle capillaries. We therefore examined whether changes in capillary flow patterns and hematocrit among open capillaries can account for oxygen extraction in muscle across orders-of-magnitude changes in blood flow. Our four-compartment model of oxygen extraction in muscle confirms this notion and provides a framework for quantifying the impact of changes in microvascular function on muscle oxygenation in health and disease. Our results underscore the importance of capillary function for oxygen extraction in muscle tissue as first proposed by Krogh. While Krogh’s model calculations still hold, our model predictions support that capillary recruitment can be viewed in the context of continuous, rather than binary, erythrocyte distributions among capillaries. NEW & NOTEWORTHY Oxygen extraction in working muscle is extremely efficient in view of single capillaries properties. The underlying mechanisms have been widely debated. Here, we develop a four-compartment model to quantify the influence of each of the hypothesized mechanisms on muscle oxygenation. Our results show that changes in capillary flow pattern and hematocrit can account for the high oxygen extraction observed in working muscle, while capillary recruitment is not required to account for these extraction properties.
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Affiliation(s)
- Hugo Angleys
- Center of Functionally Integrative Neuroscience and MindLab, Aarhus University, Aarhus, Denmark
| | - Leif Østergaard
- Center of Functionally Integrative Neuroscience and MindLab, Aarhus University, Aarhus, Denmark
- Department of Neuroradiology, Aarhus University Hospital, Aarhus, Denmark
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