1
|
Kaur A, Singh S, Mujwar S, Singh TG. Molecular Mechanisms Underlying the Therapeutic Potential of Plant-Based α-Amylase Inhibitors for Hyperglycemic Control in Diabetes. Curr Diabetes Rev 2025; 21:e020724231486. [PMID: 38956911 DOI: 10.2174/0115733998304373240611110224] [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: 02/17/2024] [Revised: 05/14/2024] [Accepted: 05/30/2024] [Indexed: 07/04/2024]
Abstract
BACKGROUND Diabetes mellitus (DM), arising from pancreatic β-cell dysfunction and disrupted alpha-amylase secretion, manifests as hyperglycemia. Synthetic inhibitors of alphaamylase like acarbose manage glucose but pose adverse effects, prompting interest in plantderived alternatives rich in antioxidants and anti-inflammatory properties. OBJECTIVE The current review investigates plant-based alpha-amylase inhibitors, exploring their potential therapeutic roles in managing DM. Focusing on their ability to modulate postprandial hyperglycemia by regulating alpha-amylase secretion, it assesses their efficacy, health benefits, and implications for diabetes treatment. METHODS This review examines plant-derived alpha-amylase inhibitors as prospective diabetic mellitus treatments using PubMed, Google Scholar, and Scopus data. RESULTS Plant-derived inhibitors, including A. deliciosa, B. egyptiaca, and N. nucifera, exhibit anti-inflammatory and antioxidant properties, effectively reducing alpha-amylase levels in diabetic conditions. Such alpha-amylase inhibitors showed promising alternative treatment in managing diabetes with reduced adverse effects. CONCLUSION The current literature concludes that plant-derived alpha-amylase inhibitors present viable therapeutic avenues for diabetes management by modulating alpha-amylase secretion by regulating inflammatory, oxidative stress, and apoptotic mechanisms involved in the pathogenesis of diabetes. Further investigation into their formulations and clinical efficacy may reveal their more comprehensive diabetes therapeutic significance, emphasizing their potential impact on glucose regulation and overall health.
Collapse
Affiliation(s)
- Amritpal Kaur
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Shareen Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Somdutt Mujwar
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India
| |
Collapse
|
2
|
Boisclair YR, Giesy SL. Endocrine adaptations to demanding physiological states in ruminants. J Dairy Sci 2024:S0022-0302(24)01377-8. [PMID: 39647618 DOI: 10.3168/jds.2024-25799] [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: 09/30/2024] [Accepted: 11/11/2024] [Indexed: 12/10/2024]
Abstract
Highly productive ruminants rely on hormonally driven adaptations to prioritize the use of limiting nutrients during the demanding phases of the pregnancy-lactation cycle. Glucose, the predominant oxidative fuel of fetal life and the absolute precursor of mammary lactose synthesis, illustrates the need and benefit of such adaptations. Endocrine mechanisms such as insulin resistance and/or hypoinsulinemia favor the diversion of maternal glucose to the placenta or mammary gland where uptake is independent of insulin. Research in dairy cows in the 1980s and 1990s identified growth hormone as a peripherally acting signal opposing the effects of insulin. The following decades have seen the discovery of a new generation of signals secreted almost exclusively by adipose tissue, skeletal muscle or liver, dynamically regulated by metabolic challenges, and engaged in cross-organ communication. The understanding of these signals in the coordination of metabolism in ruminants has been limited by the availability of assays to measure their circulating concentrations and materials to perform functional studies. Nevertheless, emerging data point to their importance during demanding physiological states in ruminants, including early lactation in dairy cows and late pregnancy in sheep. Examples include modulation of insulin action by liver-derived fibroblast growth factor 21 (FGF21) and regulation of energy allocation among tissues by the action of the adipose-derived hormone leptin via its ability to control the hypothalamic-pituitary-thyroid axis. Recent studies investigating the regulation and action of FGF21 and leptin in dairy cows and sheep will be used to illustrate the potential of recently discovered signals to coordinate metabolism during physiologically demanding states such as early lactation.
Collapse
Affiliation(s)
- Y R Boisclair
- Department of Animal Science, Cornell University, Ithaca, New York 14853.
| | - S L Giesy
- Department of Animal Science, Cornell University, Ithaca, New York 14853
| |
Collapse
|
3
|
Abdalla MMI. Advancing diabetes management: Exploring pancreatic beta-cell restoration's potential and challenges. World J Gastroenterol 2024; 30:4339-4353. [PMID: 39494103 PMCID: PMC11525866 DOI: 10.3748/wjg.v30.i40.4339] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/27/2024] [Revised: 09/05/2024] [Accepted: 09/24/2024] [Indexed: 10/16/2024] Open
Abstract
Diabetes mellitus, characterized by chronic hyperglycemia due to insulin deficiency or resistance, poses a significant global health burden. Central to its pathogenesis is the dysfunction or loss of pancreatic beta cells, which are res-ponsible for insulin production. Recent advances in beta-cell regeneration research offer promising strategies for diabetes treatment, aiming to restore endogenous insulin production and achieve glycemic control. This review explores the physiological basis of beta-cell function, recent scientific advan-cements, and the challenges in translating these findings into clinical applications. It highlights key developments in stem cell therapy, gene editing technologies, and the identification of novel regenerative molecules. Despite the potential, the field faces hurdles such as ensuring the safety and long-term efficacy of regen-erative therapies, ethical concerns around stem cell use, and the complexity of beta-cell differentiation and integration. The review highlights the importance of interdisciplinary collaboration, increased funding, the need for patient-centered approaches and the integration of new treatments into comprehensive care strategies to overcome these challenges. Through continued research and collaboration, beta-cell regeneration holds the potential to revolutionize diabetes care, turning a chronic condition into a manageable or even curable disease.
Collapse
Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
| |
Collapse
|
4
|
Dalle S, Abderrahmani A. Receptors and Signaling Pathways Controlling Beta-Cell Function and Survival as Targets for Anti-Diabetic Therapeutic Strategies. Cells 2024; 13:1244. [PMID: 39120275 PMCID: PMC11311556 DOI: 10.3390/cells13151244] [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: 06/18/2024] [Revised: 07/19/2024] [Accepted: 07/21/2024] [Indexed: 08/10/2024] Open
Abstract
Preserving the function and survival of pancreatic beta-cells, in order to achieve long-term glycemic control and prevent complications, is an essential feature for an innovative drug to have clinical value in the treatment of diabetes. Innovative research is developing therapeutic strategies to prevent pathogenic mechanisms and protect beta-cells from the deleterious effects of inflammation and/or chronic hyperglycemia over time. A better understanding of receptors and signaling pathways, and of how they interact with each other in beta-cells, remains crucial and is a prerequisite for any strategy to develop therapeutic tools aimed at modulating beta-cell function and/or mass. Here, we present a comprehensive review of our knowledge on membrane and intracellular receptors and signaling pathways as targets of interest to protect beta-cells from dysfunction and apoptotic death, which opens or could open the way to the development of innovative therapies for diabetes.
Collapse
Affiliation(s)
- Stéphane Dalle
- Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), 34094 Montpellier, France
| | - Amar Abderrahmani
- Université Lille, Centre National de la Recherche Scientifique (CNRS), Centrale Lille, Université Polytechnique Hauts-de-France, UMR 8520, IEMN, F59000 Lille, France
| |
Collapse
|
5
|
Ngema M, Xulu ND, Ngubane PS, Khathi A. Pregestational Prediabetes Induces Maternal Hypothalamic-Pituitary-Adrenal (HPA) Axis Dysregulation and Results in Adverse Foetal Outcomes. Int J Mol Sci 2024; 25:5431. [PMID: 38791468 PMCID: PMC11122116 DOI: 10.3390/ijms25105431] [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: 03/26/2024] [Revised: 04/24/2024] [Accepted: 04/29/2024] [Indexed: 05/26/2024] Open
Abstract
Maternal type 2 diabetes mellitus (T2DM) has been shown to result in foetal programming of the hypothalamic-pituitary-adrenal (HPA) axis, leading to adverse foetal outcomes. T2DM is preceded by prediabetes and shares similar pathophysiological complications. However, no studies have investigated the effects of maternal prediabetes on foetal HPA axis function and postnatal offspring development. Hence, this study investigated the effects of pregestational prediabetes on maternal HPA axis function and postnatal offspring development. Pre-diabetic (PD) and non-pre-diabetic (NPD) female Sprague Dawley rats were mated with non-prediabetic males. After gestation, male pups born from the PD and NPD groups were collected. Markers of HPA axis function, adrenocorticotropin hormone (ACTH) and corticosterone, were measured in all dams and pups. Glucose tolerance, insulin and gene expressions of mineralocorticoid (MR) and glucocorticoid (GR) receptors were further measured in all pups at birth and their developmental milestones. The results demonstrated increased basal concentrations of ACTH and corticosterone in the dams from the PD group by comparison to NPD. Furthermore, the results show an increase basal ACTH and corticosterone concentrations, disturbed MR and GR gene expression, glucose intolerance and insulin resistance assessed via the Homeostasis Model Assessment (HOMA) indices in the pups born from the PD group compared to NPD group at all developmental milestones. These observations reveal that pregestational prediabetes is associated with maternal dysregulation of the HPA axis, impacting offspring HPA axis development along with impaired glucose handling.
Collapse
Affiliation(s)
| | | | | | - Andile Khathi
- School of Laboratory Medicine & Medical Sciences, University of KwaZulu-Natal, Westville, Private Bag X54001, Durban 4041, KwaZulu Natal, South Africa; (M.N.); (N.D.X.); (P.S.N.)
| |
Collapse
|
6
|
Šterk M, Zhang Y, Pohorec V, Leitgeb EP, Dolenšek J, Benninger RKP, Stožer A, Kravets V, Gosak M. Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis. PLoS Comput Biol 2024; 20:e1012130. [PMID: 38739680 PMCID: PMC11115366 DOI: 10.1371/journal.pcbi.1012130] [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] [Received: 01/03/2024] [Revised: 05/23/2024] [Accepted: 05/02/2024] [Indexed: 05/16/2024] Open
Abstract
Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes. Recently, innovative approaches, such as integrating multicellular calcium imaging with network analysis, have emerged for a quantitative assessment of the cellular activity in islets. However, different groups use distinct experimental preparations, microscopic techniques, apply different methods to process the measured signals and use various methods to derive functional connectivity patterns. This makes comparisons between findings and their integration into a bigger picture difficult and has led to disputes in functional connectivity interpretations. To address these issues, we present here a systematic analysis of how different approaches influence the network representation of islet activity. Our findings show that the choice of methods used to construct networks is not crucial, although care is needed when combining data from different islets. Conversely, the conclusions drawn from network analysis can be heavily affected by the pre-processing of the time series, the type of the oscillatory component in the signals, and by the experimental preparation. Our tutorial-like investigation aims to resolve interpretational issues, reconcile conflicting views, advance functional implications, and encourage researchers to adopt connectivity analysis. As we conclude, we outline challenges for future research, emphasizing the broader applicability of our conclusions to other tissues exhibiting complex multicellular dynamics.
Collapse
Affiliation(s)
- Marko Šterk
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Yaowen Zhang
- Department of Pediatrics, Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America
| | - Viljem Pohorec
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | | | - Jurij Dolenšek
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Richard K. P. Benninger
- Department of Bioengineering, Barbara Davis Center for Diabetes, Aurora, Colorado, United States of America
- Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States of America
| | - Andraž Stožer
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
| | - Vira Kravets
- Department of Pediatrics, Department of Bioengineering, University of California, San Diego, La Jolla, California, United States of America
- Department of Bioengineering, Jacobs School of Engineering, University of California, San Diego, La Jolla, California, United States of America
| | - Marko Gosak
- Faculty of Natural Sciences and Mathematics, University of Maribor, Maribor, Slovenia
- Faculty of Medicine, University of Maribor, Maribor, Slovenia
- Alma Mater Europaea, Maribor
| |
Collapse
|
7
|
Dos Reis Araujo T, Alves BL, Dos Santos LMB, Gonçalves LM, Carneiro EM. Association between protein undernutrition and diabetes: Molecular implications in the reduction of insulin secretion. Rev Endocr Metab Disord 2024; 25:259-278. [PMID: 38048021 DOI: 10.1007/s11154-023-09856-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/20/2023] [Indexed: 12/05/2023]
Abstract
Undernutrition is still a recurring nutritional problem in low and middle-income countries. It is directly associated with the social and economic sphere, but it can also negatively impact the health of the population. In this sense, it is believed that undernourished individuals may be more susceptible to the development of non-communicable diseases, such as diabetes mellitus, throughout life. This hypothesis was postulated and confirmed until today by several studies that demonstrate that experimental models submitted to protein undernutrition present alterations in glycemic homeostasis linked, in part, to the reduction of insulin secretion. Therefore, understanding the changes that lead to a reduction in the secretion of this hormone is essential to prevent the development of diabetes in undernourished individuals. This narrative review aims to describe the main molecular changes already characterized in pancreatic β cells that will contribute to the reduction of insulin secretion in protein undernutrition. So, it will provide new perspectives and targets for postulation and action of therapeutic strategies to improve glycemic homeostasis during this nutritional deficiency.
Collapse
Affiliation(s)
- Thiago Dos Reis Araujo
- Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Carl Von Linnaeus Bloco Z, Campinas, SP, Cep: 13083-864, Brazil
| | - Bruna Lourençoni Alves
- Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Carl Von Linnaeus Bloco Z, Campinas, SP, Cep: 13083-864, Brazil
| | - Lohanna Monali Barreto Dos Santos
- Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Carl Von Linnaeus Bloco Z, Campinas, SP, Cep: 13083-864, Brazil
| | - Luciana Mateus Gonçalves
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, USA
| | - Everardo Magalhães Carneiro
- Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas, Carl Von Linnaeus Bloco Z, Campinas, SP, Cep: 13083-864, Brazil.
| |
Collapse
|
8
|
Schalla MA, Taché Y, Stengel A. Editorial: Autonomic regulation of enteroendocrine peptides in health and diseases. Peptides 2023:171038. [PMID: 37295652 DOI: 10.1016/j.peptides.2023.171038] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Affiliation(s)
- Martha A Schalla
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany; Department of Gynecology and Obstetrics, HELIOS Kliniken GmbH, Rottweil, Germany
| | - Yvette Taché
- VA Greater Los Angeles Healthcare System, Los Angeles, California, USA; Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, Digestive Diseases Research Center (DDRC), Center for Neurobiology of Stress and Resilience (CNSR), University of California Los Angeles, Los Angeles, California, USA
| | - Andreas Stengel
- Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, Tübingen, Germany; Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine; Charite - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.
| |
Collapse
|
9
|
Rinaldi E, van der Heide FC, Bonora E, Trombetta M, Zusi C, Kroon AA, Schram MT, van der Kallen CJ, Wesselius A, Bonadonna R, Mari A, Schalkwijk CG, van Greevenbroek MM, Stehouwer CDA. Lower heart rate variability, an index of worse autonomic function, is associated with worse beta cell response to a glycemic load in vivo-The Maastricht Study. Cardiovasc Diabetol 2023; 22:105. [PMID: 37143089 PMCID: PMC10161476 DOI: 10.1186/s12933-023-01837-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 04/19/2023] [Indexed: 05/06/2023] Open
Abstract
OBJECTIVE We investigated, using population-based data, whether worse autonomic function, estimated from lower 24-hour heart rate variability (HRV), was associated with beta cell function, assessed from beta cell response during an oral glucose tolerance test (OGTT). RESEARCH DESIGN AND METHODS We used cross-sectional data from The Maastricht Study, a population-based cohort study (N = 2,007; age, mean ± SD:60 ± 8 years; 52% men; and 24% with type 2 diabetes). We used linear regression analyses with adjustment for potential confounders (demographic, cardiovascular, and lifestyle factors) to study the associations of time- and frequency-domain HRV (composite scores) with overall beta cell response (estimated from a composite score calculated from: C-peptidogenic index, overall insulin secretion, beta cell glucose sensitivity, beta cell potentiation factor, and beta cell rate sensitivity). In addition, we tested for interaction by sex and glucose metabolism status. RESULTS After full adjustment, lower time- and frequency-domain HRV was significantly associated with lower overall beta cell response composite score (standardized beta, -0.055 [-0.098; -0.011] and - 0.051 [-0.095; -0.007], respectively). These associations were not modified by sex and there was no consistent pattern of interaction by glucose metabolism status. CONCLUSION The present etiological study found that worse autonomic function, estimated from lower HRV, was associated with worse beta cell function, estimated from a composite score in a population-based sample which covered the entire spectrum of glucose metabolism. Hence, autonomic dysfunction may contribute to beta cell dysfunction and, ultimately, to the alteration of glucose metabolism status from normal glucose metabolism to prediabetes and type 2 diabetes.
Collapse
Affiliation(s)
- Elisabetta Rinaldi
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro 10, Verona, 37134, Italy.
| | - Frank Ct van der Heide
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| | - Enzo Bonora
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro 10, Verona, 37134, Italy
| | - Maddalena Trombetta
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro 10, Verona, 37134, Italy
| | - Chiara Zusi
- Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, University of Verona, Policlinico GB Rossi, Piazzale L.A. Scuro 10, Verona, 37134, Italy
| | - Abraham A Kroon
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| | - Miranda T Schram
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
- Heart and Vascular Centre, MUMC+, Maastricht, the Netherlands
| | - Carla Jh van der Kallen
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| | - Anke Wesselius
- Department of Epidemiology, UM, Maastricht, the Netherlands
- NUTRIM School for Nutrition and Translational Research in Metabolism, UM, Maastricht, the Netherlands
| | - Riccardo Bonadonna
- Department of Medicine and Surgery, University of Parma, Parma, Italy
- Division of Endocrinology and Metabolic Diseases, Azienda Ospedaliera-Universitaria di Parma, Parma, Italy
| | - Andrea Mari
- Institute of Neuroscience, National Research Council, Padua, Italy
| | - Casper G Schalkwijk
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| | - Marleen Mj van Greevenbroek
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| | - Coen DA Stehouwer
- CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, the Netherlands
- Department of Internal Medicine, Maastricht University Medical Centre+ (MUMC+), Maastricht, the Netherlands
| |
Collapse
|
10
|
Hall LG, Thyfault JP, Johnson JD. Exercise and inactivity as modifiers of β cell function and type 2 diabetes risk. J Appl Physiol (1985) 2023; 134:823-839. [PMID: 36759159 PMCID: PMC10042613 DOI: 10.1152/japplphysiol.00472.2022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 01/31/2023] [Accepted: 01/31/2023] [Indexed: 02/11/2023] Open
Abstract
Exercise and regular physical activity are beneficial for the prevention and management of metabolic diseases such as obesity and type 2 diabetes, whereas exercise cessation, defined as deconditioning from regular exercise or physical activity that has lasted for a period of months to years, can lead to metabolic derangements that drive disease. Adaptations to the insulin-secreting pancreatic β-cells are an important benefit of exercise, whereas less is known about how exercise cessation affects these cells. Our aim is to review the impact that exercise and exercise cessation have on β-cell function, with a focus on the evidence from studies examining glucose-stimulated insulin secretion (GSIS) using gold-standard techniques. Potential mechanisms by which the β-cell adapts to exercise, including exerkine and incretin signaling, autonomic nervous system signaling, and changes in insulin clearance, will also be explored. We will highlight areas for future research.
Collapse
Affiliation(s)
- Liam G Hall
- Department of Cellular and Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada
| | - John P Thyfault
- Department of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, Kansas, United States
- Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, United States
- KU Diabetes Institute, University of Kansas Medical Center, Kansas City, Kansas, United States
| | - James D Johnson
- Department of Cellular and Physiological Sciences, Life Sciences Institute, The University of British Columbia, Vancouver, British Columbia, Canada
| |
Collapse
|