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Zhang N, Liu J, Wang M, Guo X, Fan B, Wang F. Potato protease inhibitor II prevents obesity by inducing browning of white adipose tissue in mice via β 3 adrenergic receptor signaling pathway. Phytother Res 2022; 36:3885-3899. [PMID: 36017979 DOI: 10.1002/ptr.7451] [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: 06/17/2021] [Revised: 03/08/2022] [Accepted: 03/08/2022] [Indexed: 11/09/2022]
Abstract
There are currently few effective and safe pharmacologic means for inducing beige adipogenesis in humans. This study highlights the role of potato protease inhibitor II (PPI II) in regulating the browning of adipose tissue. The in vitro results showed that PPI II increased the expression of the uncoupling protein 1 (UCP1) protein and gene and beige-specific genes, including Cd137, Cited1, Tbx1, and Tmem26 in vitro. PPI II treatment for three months in diet-induced obesity mice increased the levels of the UCP1 protein in white adipose tissue, causing elevated energy expenditure, thus preventing obesity and improving glucose tolerance. Mechanistic studies further revealed that PPI II regulated the abundance and activity of β3 adrenergic receptor (β3 -AR) in white adipocytes. Chemical-inhibition experiments revealed the crucial role of β3 -AR-dependent protein kinase A (PKA)-p38 kinase (p38)/extracellular signal-related kinase1/2 (ERK1/2) signaling in PPI II-mediated browning program of white adipose tissues. In summary, our findings highlight the role of PPI II in beige adipocyte differentiation and thermogenesis and provide new insights into its use in preventing obesity.
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Affiliation(s)
- Nana Zhang
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Jianlin Liu
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Minjie Wang
- School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, China
| | - Xinxin Guo
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Bei Fan
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Fengzhong Wang
- Key Laboratory of Agro-Products Processing, Ministry of Agriculture, Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences, Beijing, China
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Jiménez-Munoz L, Tsochatzis ED, Corredig M. Impact of the Structural Modifications of Potato Protein in the Digestibility Process under Semi-Dynamic Simulated Human Gastrointestinal In Vitro System. Nutrients 2022; 14:nu14122505. [PMID: 35745236 PMCID: PMC9230451 DOI: 10.3390/nu14122505] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Revised: 06/11/2022] [Accepted: 06/14/2022] [Indexed: 02/01/2023] Open
Abstract
The raising consumer demand for plant-derived proteins has led to an increased production of alternative protein ingredients with varying processing histories. In this study, we used a commercially available potato protein ingredient with a nutritionally valuable amino acid profile and high technological functionality to evaluate if the digestibility of a suspension with the same composition is affected by differences in the structure. Four isocaloric (4% protein, w/w) matrices (suspension, gel, foam and heat-set foam) were prepared and their gastrointestinal fate was followed utilizing a semi-dynamic in vitro digestion model. The microstructure was observed by confocal laser scanning microscopy, protein breakdown was tested by electrophoresis and free amino acids after intestinal digestion was estimated using liquid chromatography/triple-quadruple-mass spectrometry (LC-TQMS). The heat-treated samples showed a higher degree of hydrolysis and lower trypsin inhibitory activity than the non-heat-treated samples. An in vitro digestible indispensable amino acid score was calculated based on experimental data, showing a value of 0.9 based on sulfur amino acids/valine as the limiting amino acids. The heated samples also showed a slower gastric emptying rate. The study highlights the effect of the food matrix on the distribution of the peptides created during various stages of gastric emptying.
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Affiliation(s)
- Luis Jiménez-Munoz
- Department of Food Science, CiFOOD Center for Innovative Foods, Aarhus University, Agro Food Park 48, 8200 Aarhus, Denmark; (E.D.T.); (M.C.)
- Correspondence: author:
| | - Emmanouil D. Tsochatzis
- Department of Food Science, CiFOOD Center for Innovative Foods, Aarhus University, Agro Food Park 48, 8200 Aarhus, Denmark; (E.D.T.); (M.C.)
- European Food Safety Authority-EFSA, Via Carlo Magno 1A, 43146 Parma, Italy
| | - Milena Corredig
- Department of Food Science, CiFOOD Center for Innovative Foods, Aarhus University, Agro Food Park 48, 8200 Aarhus, Denmark; (E.D.T.); (M.C.)
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Flechtner-Mors M, Thoma U, Wittmann R, Boehm BO, Mors M, Steinacker JM, Schumann U. The Effect of Potato Protease Inhibitor II on Gastrointestinal Hormones and Satiety in Humans During Weight Reduction. Diabetes Metab Syndr Obes 2020; 13:521-534. [PMID: 32161479 PMCID: PMC7049780 DOI: 10.2147/dmso.s201853] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Accepted: 12/07/2019] [Indexed: 12/16/2022] Open
Abstract
CONTEXT It is questioned whether the potato protein protease inhibitor II (PI2) reduces appetite and exerts effects on the satiety hormone cholecystokinin (CCK). OBJECTIVE To investigate PI2 impact on gastrointestinal hormones and appetite measures during weight reduction. DESIGN In a randomized, placebo-controlled trial over 20 weeks, fifty-two overweight/obese participants (BMI 25.2-38.0 kg/m2) received a protein-rich diet (30%) adjusted to 500 kcal below their individual daily needs. Subjects ingested a capsule containing either PI2 (150 mg) or placebo twice daily 1 hr before lunch and dinner. At week 0 and week 10 participants joined breakfast test meals to determine CCK, GLP-1, ghrelin, leptin, glucose and insulin concentrations in a time course experimental manner. Appetite sensations were measured on test meal days and in week 4, 9, 14 and 19 using visual analogue scales. RESULTS Weight loss at week 10 and 20 in the PI2 group was 4.3±3.1 kg and 5.6±4.1 kg, in the control group: 4.7±4.0 kg and 6.8±3.7 kg. A significant effect of PI2 on circulating CCK levels was observed at week 10. The other hormones were unaffected by PI2. At week 10, PI2 group subjects showed higher satiety and decreased desire to eat compared to placebo. During study duration, PI2 showed a significant impact on appetite ratings prior to lunch, one hour before dinner and just before dinner. CONCLUSION PI2 increased circulating CCK plasma levels during the diet intervention. Likewise, PI2 modulated appetite sensation from week 4 to 20. The study demonstrated that the PI2 can modulate a key satiety signal.
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Affiliation(s)
- Marion Flechtner-Mors
- University Medical Center Ulm, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, Ulm, Germany
- Correspondence: Marion Flechtner-Mors Department of Internal Medicine II, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, Leimgrubenweg 14, Ulm89075, GermanyTel + 49 731 50045330Fax + 49 731 50045333 Email
| | - Ulrike Thoma
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Regina Wittmann
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Bernhard O Boehm
- Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
- Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, Singapore
- Imperial College London, London, UK
| | - Mona Mors
- University Medical Center Ulm, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, Ulm, Germany
| | - Jürgen M Steinacker
- University Medical Center Ulm, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, Ulm, Germany
| | - Uwe Schumann
- University Medical Center Ulm, Division of Sports and Rehabilitation Medicine, University Hospital Ulm, Ulm, Germany
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Zhu Y, Lasrado JA, Hu J. Potato protease inhibitor II suppresses postprandial appetite in healthy women: a randomized double-blind placebo-controlled trial. Food Funct 2017; 8:1988-1993. [PMID: 28485429 DOI: 10.1039/c6fo01803c] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
The effect of potato protease inhibitor II (PI2) on postprandial appetite was examined in a randomized double-blind placebo-controlled cross-over trial involving 44 healthy women. In separate test sessions, participants consumed a capsule containing placebo or potato extract standardized to 15 or 30 mg PI2 after overnight fasting. One hour later, a standard 390 kcal breakfast was served. At regular time points during the three-hour period after breakfast, appetite was measured by visual analog scales, and blood samples were collected for assay of cholecystokinin, insulin, and glucose. Compared with the placebo, consumption of 15 mg or 30 mg PI2 one hour prior to a standard breakfast meal resulted in significantly lower postprandial hunger, desire to eat, and prospective consumption, as well as significantly higher postprandial fullness. Consumption of 15 mg PI2 also resulted in significantly higher postprandial plasma levels of cholecystokinin compared with the placebo. No significant main effect of treatment was found on insulin and glucose. No adverse events were reported. Results from the study revealed that consumption of potato PI2 at the examined doses was well tolerated, suppressed subjective appetite in a dose-dependent manner, and increased plasma concentrations of cholecystokinin. Future studies are needed to evaluate the long-term effect of PI2 on body weight.
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Affiliation(s)
- Yong Zhu
- Kemin Foods, L.C., Des Moines, Iowa 50317, USA.
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Visvanathan R, Jayathilake C, Chaminda Jayawardana B, Liyanage R. Health-beneficial properties of potato and compounds of interest. JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE 2016; 96:4850-4860. [PMID: 27301296 DOI: 10.1002/jsfa.7848] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 10/28/2015] [Accepted: 06/06/2016] [Indexed: 06/06/2023]
Abstract
Potatoes have shown promising health-promoting properties in human cell culture, experimental animal and human clinical studies, including antioxidant, hypocholesterolemic, anti-inflammatory, antiobesity, anticancer and antidiabetic effects. Compounds present such as phenolics, fiber, starch and proteins as well as compounds considered antinutritional such as glycoalkaloids, lectins and proteinase inhibitors are believed to contribute to the health benefits of potatoes. However, epidemiological studies exploring the role of potatoes in human health have been inconclusive. Some studies support a protective effect of potato consumption in weight management and diabetes, while other studies demonstrate no effect and a few suggest a negative effect. As there are many biological activities attributed to the compounds present in potato, some of which could be beneficial or detrimental depending on specific circumstances, a long-term study investigating the association between potato consumption and diabetes, obesity, cardiovascular disease and cancer while controlling for fat intake is needed. © 2016 Society of Chemical Industry.
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Affiliation(s)
- Rizliya Visvanathan
- Division of Nutritional Biochemistry, National Institute of Fundamental Studies, Kandy, Sri Lanka
| | - Chathuni Jayathilake
- Division of Nutritional Biochemistry, National Institute of Fundamental Studies, Kandy, Sri Lanka
| | | | - Ruvini Liyanage
- Division of Nutritional Biochemistry, National Institute of Fundamental Studies, Kandy, Sri Lanka.
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Ku SK, Sung SH, Choung JJ, Choi JS, Shin YK, Kim JW. Anti-obesity and anti-diabetic effects of a standardized potato extract in ob/ ob mice. Exp Ther Med 2016; 12:354-364. [PMID: 27347062 DOI: 10.3892/etm.2016.3256] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2015] [Accepted: 03/15/2016] [Indexed: 12/16/2022] Open
Abstract
The potato (Solanum tuberosum) has been cultivated globally for food for millenia. Potato contains proteinase inhibitor II, which catalyzes the release of cholecystokinin (CCK), leading to delayed gastric emptying in humans. The present study investigated the anti-obesity effects of Slendesta™ Potato Extract (SLD), a standardized potato extract containing 5% proteinase inhibitor II, in the ob/ob obese mice. Three doses of SLD (50, 150 or 300 mg/kg) were orally administered to ob/ob mice once a day for 28 days, whereas control mice were administered distilled water. Four weeks after SLD treatment, the changes in body weight, food consumption, epididymal fat weight, serum chemistry, insulin, leptin and adiponectin contents, and fat histopathology were determined and compared with ob/ob mice treated with 750 mg/kg conjugate linoleic acid. As a result of SLD treatment in the obese mice, body weight, food consumption, epididymal fat, serum biochemistry, histomorphological changes of fat and pancreas were significantly and dose-dependently decreased compared with ob/ob control mice. These obesity and type 2 diabetes associated alterations were significantly inhibited after SLD treatment for 28 days. Thus, the present results indicate that SLD has potential as an alternative therapeutic agent for obesity.
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Affiliation(s)
- Sae Kwang Ku
- Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan-Si, Gyeongsanbuk-Do 712-715, Republic of Korea
| | - Soo Hyun Sung
- Aribio, Inc., Byeoksan Digital Valley, Suite 1004, Yeongdeungpo-Gu, Seoul 150-095, Republic of Korea
| | | | - Jae-Suk Choi
- Division of Bioindustry, College of Medical and Life Sciences, Silla University, Sasang-Gu, Busan 617-736, Republic of Korea
| | - Yong Kook Shin
- Department of Natural Medicine Resources, Semyung University, Jecheon-Si, Chungcheongbuk-Do 390-711, Republic of Korea
| | - Joo Wan Kim
- Aribio, Inc., Byeoksan Digital Valley, Suite 1004, Yeongdeungpo-Gu, Seoul 150-095, Republic of Korea
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Li JL, Li M, Tian JX, Pang B, Tong XL. Methods for clinical evaluation of diabetic gastroparesis. Shijie Huaren Xiaohua Zazhi 2013; 21:3198-3203. [DOI: 10.11569/wcjd.v21.i30.3198] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
An effective clinical assessment method is necessary for the development of new drugs. Currently, main methods for clinical evaluation of diabetic gastroparesis (DGP) include evaluation of gastric emptying, patients' subjective evaluation of disease severity and the change in pathogenic factors. However, there are many problems that need to address; the methods for the evaluation of gastric emptying have not been widely used, there is no uniform standard for the patients' subjective evaluation, and the pathogenic factors for DGP are not completely clear. In this article we will review the methods for clinical evaluation of DGP, with the emphasis on the above problems.
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't Hart LM, Fritsche A, Nijpels G, van Leeuwen N, Donnelly LA, Dekker JM, Alssema M, Fadista J, Carlotti F, Gjesing AP, Palmer CNA, van Haeften TW, Herzberg-Schäfer SA, Simonis-Bik AMC, Houwing-Duistermaat JJ, Helmer Q, Deelen J, Guigas B, Hansen T, Machicao F, Willemsen G, Heine RJ, Kramer MHH, Holst JJ, de Koning EJP, Häring HU, Pedersen O, Groop L, de Geus EJC, Slagboom PE, Boomsma DI, Eekhoff EMW, Pearson ER, Diamant M. The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway. Diabetes 2013; 62:3275-81. [PMID: 23674605 PMCID: PMC3749354 DOI: 10.2337/db13-0227] [Citation(s) in RCA: 77] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The incretin hormone glucagon-like peptide 1 (GLP-1) promotes glucose homeostasis and enhances β-cell function. GLP-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which inhibit the physiological inactivation of endogenous GLP-1, are used for the treatment of type 2 diabetes. Using the Metabochip, we identified three novel genetic loci with large effects (30-40%) on GLP-1-stimulated insulin secretion during hyperglycemic clamps in nondiabetic Caucasian individuals (TMEM114; CHST3 and CTRB1/2; n = 232; all P ≤ 8.8 × 10(-7)). rs7202877 near CTRB1/2, a known diabetes risk locus, also associated with an absolute 0.51 ± 0.16% (5.6 ± 1.7 mmol/mol) lower A1C response to DPP-4 inhibitor treatment in G-allele carriers, but there was no effect on GLP-1 RA treatment in type 2 diabetic patients (n = 527). Furthermore, in pancreatic tissue, we show that rs7202877 acts as expression quantitative trait locus for CTRB1 and CTRB2, encoding chymotrypsinogen, and increases fecal chymotrypsin activity in healthy carriers. Chymotrypsin is one of the most abundant digestive enzymes in the gut where it cleaves food proteins into smaller peptide fragments. Our data identify chymotrypsin in the regulation of the incretin pathway, development of diabetes, and response to DPP-4 inhibitor treatment.
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Affiliation(s)
- Leen M 't Hart
- Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, the Netherlands.
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EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific Opinion on the substantiation of a health claim related to Slendesta® Potato Extract and reduction of body weight pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J 2013. [DOI: 10.2903/j.efsa.2013.3083] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022] Open
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10
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Reduced Energy Intake and Weight Loss on a Legume-Enriched Diet Lead to Improvements in Biomarkers Related to Chronic Disease. TOP CLIN NUTR 2011. [DOI: 10.1097/tin.0b013e3182260eb3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Jahan-Mihan A, Luhovyy BL, El Khoury D, Anderson GH. Dietary proteins as determinants of metabolic and physiologic functions of the gastrointestinal tract. Nutrients 2011; 3:574-603. [PMID: 22254112 PMCID: PMC3257691 DOI: 10.3390/nu3050574] [Citation(s) in RCA: 139] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2011] [Revised: 04/29/2011] [Accepted: 05/09/2011] [Indexed: 02/07/2023] Open
Abstract
Dietary proteins elicit a wide range of nutritional and biological functions. Beyond their nutritional role as the source of amino acids for protein synthesis, they are instrumental in the regulation of food intake, glucose and lipid metabolism, blood pressure, bone metabolism and immune function. The interaction of dietary proteins and their products of digestion with the regulatory functions of the gastrointestinal (GI) tract plays a dominant role in determining the physiological properties of proteins. The site of interaction is widespread, from the oral cavity to the colon. The characteristics of proteins that influence their interaction with the GI tract in a source-dependent manner include their physico-chemical properties, their amino acid composition and sequence, their bioactive peptides, their digestion kinetics and also the non-protein bioactive components conjugated with them. Within the GI tract, these products affect several regulatory functions by interacting with receptors releasing hormones, affecting stomach emptying and GI transport and absorption, transmitting neural signals to the brain, and modifying the microflora. This review discusses the interaction of dietary proteins during digestion and absorption with the physiological and metabolic functions of the GI tract, and illustrates the importance of this interaction in the regulation of amino acid, glucose, lipid metabolism, and food intake.
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Affiliation(s)
- Alireza Jahan-Mihan
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
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12
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Komarnytsky S, Cook A, Raskin I. Potato protease inhibitors inhibit food intake and increase circulating cholecystokinin levels by a trypsin-dependent mechanism. Int J Obes (Lond) 2010; 35:236-43. [PMID: 20820171 PMCID: PMC3033477 DOI: 10.1038/ijo.2010.192] [Citation(s) in RCA: 54] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective To investigate the mechanisms underlying the satiety-promoting effects of a novel protease inhibitors concentrate derived from potato (PPIC). Methods Acute and prolonged effects of oral PPIC administration (100 mg/kg per day) on food intake, body weight, and gastric emptying were evaluated in healthy rats. Parameters of body weight, food intake, plasma glucose, insulin, and cholecystokinin (CCK) were measured. Duodenal proteolytic activity and CCK expression were determined in tissue extracts. Intestinal STC-1 cell culture model was used to investigate the direct effect of PPIC on CCK transcript level and secretion. Results Acute oral administration of PPIC reduced immediate food intake during the first two hours following the treatment, delayed gastric emptying, and decreased proteolytic activity in the duodenum. Repeated oral ingestion of PPIC reduced weight gain in male rats and significantly elevated the plasma CCK levels. Although duodenal mucosal CCK mRNA levels increased in response to PPIC administration, the concentrate failed to elevate CCK expression or release in STC-1 cells. The 14-day ascending dose range study (33 to 266 mg/kg PPIC per day) showed no adverse side effects associated with PPIC administration. Conclusion These findings provided evidence that PPIC is effective in reducing food intake and body weight gain in healthy rats when administered orally by increasing circulating CCK levels through a trypsin-dependent mechanism.
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Affiliation(s)
- S Komarnytsky
- Biotech Center, SEBS, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA.
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13
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Peters HPF, Foltz M, Kovacs EMR, Mela DJ, Schuring EAH, Wiseman SA. The effect of protease inhibitors derived from potato formulated in a minidrink on appetite, food intake and plasma cholecystokinin levels in humans. Int J Obes (Lond) 2010; 35:244-50. [PMID: 20644555 DOI: 10.1038/ijo.2010.136] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
BACKGROUND Protease inhibitor 2 derived from potato (PI2) is claimed to reduce appetite and food intake, stimulate the satiety hormone cholecystokinin (CCK) and lower postprandial glucose peaks when taken before a meal. However, current literature is inconclusive with regard to its efficacy and mechanism. Furthermore, the potential effect of PI2 on appetite motivational ratings without an immediately following meal has not previously been reported. OBJECTIVE To comprehensively test the effects of 30 mg PI2 in a minidrink on appetite ratings, subsequent food intake, and plasma CCK and glucose responses. DESIGN Minidrinks with or without 30 mg PI2 were compared in three separate substudies (A, B and C), each using a two-way, placebo-controlled, balanced-order, cross-over design and 23 or 24 subjects (mean over groups: body mass index 25.0 kg m(-2), range 22.5-30.7 kg m(-2); age 41.3, range 18-62 years). The minidrink was given (A) 120 or (B) 30 min before an ad libitum lunch or (C) 30 min before a fixed lunch. Study parameters were self-reported satiety (substudies A and C), ad libitum meal intake (substudies A and B), and (in an n=12 subset) plasma CCK and blood glucose in all substudies. All results were analyzed using analysis of covariance. Protease-inhibitory activity of the PI2-containing minidrinks was assessed under simulated gut conditions. RESULTS PI2 did not differ from control for any study parameters, in any substudy, despite confirmation of the inhibitory activity of PI2. CONCLUSIONS In this study protease inhibition using PI2 in a minidrink at a dose of 30 mg, as commercially used, had no (functional) efficacy on a range of behavioral and physiological appetite and intake control measures.
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Affiliation(s)
- H P F Peters
- Unilever Research & Development, Vlaardingen, The Netherlands.
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14
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Punkkinen J, Färkkilä M, Mätzke S, Korppi-Tommola T, Sane T, Piirilä P, Koskenpato J. Upper abdominal symptoms in patients with Type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy. Diabet Med 2008; 25:570-7. [PMID: 18445170 DOI: 10.1111/j.1464-5491.2008.02428.x] [Citation(s) in RCA: 49] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIMS Diabetic gastroparesis is a common condition occurring in some 30-50% of patients with long-term diabetes. Some studies have found a relationship between autonomic neuropathy and diabetic gastroparesis. In addition to autonomic neuropathy, acute changes in plasma glucose concentration can also affect gastric emptying. The objective was to examine the relationship between autonomic nerve function, glucose concentration, gastric emptying, and upper abdominal symptoms in Type 1 diabetic patients. METHODS Gastric emptying of solids and liquids was measured with scintigraphy in 27 patients with longstanding Type 1 diabetes with upper abdominal symptoms. Autonomic nerve function was examined by standardized cardiovascular tests, and plasma glucose concentrations were measured during scintigraphy. Severity of abdominal symptoms and quality of life were explored by validated questionnaires. RESULTS Seven patients (26%) had delayed gastric emptying of solids and three (11%) of liquids. Mean gastric half-emptying time of solids was 128 +/- 116 min and of liquids 42 +/- 30 min. Of the 26 patients undergoing tests, 16 (62%) had autonomic nerve dysfunction. Autonomic neuropathy score (1.6 +/- 1.7) correlated positively with the gastric emptying rate of solids (P = 0.006), a rate unrelated to symptom scores or plasma glucose concentrations during scintigraphy. Quality of life in patients with abdominal symptoms was lower than in the normal Finnish population. CONCLUSIONS Impaired gastric emptying of solids in patients with Type 1 diabetes is related to autonomic neuropathy, but not to actual glycaemic control. The upper abdominal symptoms observed in these patients cannot be explained, however, by impaired gastric emptying.
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Affiliation(s)
- J Punkkinen
- Department of Gastroenterology, Helsinki University Central Hospital, Helsinki, Finland.
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Intagliata N, Koch KL. Gastroparesis in type 2 diabetes mellitus: prevalence, etiology, diagnosis, and treatment. Curr Gastroenterol Rep 2007; 9:270-9. [PMID: 17883973 DOI: 10.1007/s11894-007-0030-3] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The worldwide epidemic of type 2 diabetes mellitus (T2DM) is a substantial economic and social burden. Although gastroparesis associated with type 1 diabetes mellitus (T1DM) has been recognized for years, only recently have studies shown that patients with T2DM also have high rates of gastroparesis. Individuals with T2DM constitute 90% to 95% of the diabetic population. Unique characteristics that distinguish this population are obesity, insulin resistance, and associated comorbidities. These features highlight the importance of investigating gastric emptying in individuals with T2DM and upper gastrointestinal symptoms. The purpose of this review is to examine the literature pertaining to diabetes and the effect of diabetes on gastric neuromuscular function, with a focus on T2DM. An understanding of gastric motility in T2DM is important to diagnose gastroparesis, to treat upper gastrointestinal symptoms, and to restore normal gastric motility, which may lead, in turn, to improved glucose control.
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Affiliation(s)
- Nicolas Intagliata
- Section on Gastroenterology, Wake Forest University Medical Center, Nutrition Building, E-115, Medical Center Boulevard, Winston-Salem, NC 27157, USA
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Abstract
Gastric emptying is mildly slowed in healthy aging, although generally remains within the normal range for young people. The significance of this is unclear, but may potentially influence the absorption of certain drugs, especially when a rapid effect is desired. Type 2 diabetes is common in the elderly, but there is little data regarding its natural history, prognosis, and management. This article focuses on the interactions between gastric emptying and diabetes, how each is influenced by the process of aging, and the implications for patient management.
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Affiliation(s)
- Paul Kuo
- Discipline of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
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Santiago-Maldonado IM, Phillips WT. Frequent occurrence of rapid as well as delayed gastric emptying of a corn flakes and milk meal in clinical patients with gastrointestinal symptoms. Clin Nucl Med 2007; 32:186-93. [PMID: 17314592 DOI: 10.1097/01.rlu.0000255028.99539.d3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE Early satiety, nausea and vomiting have traditionally been associated with delayed gastric emptying (GE). A study was performed to determine the frequency of rapid/delayed GE in 100 patients sequentially referred for scintigraphic GE using a corn flakes and milk meal. METHODS AND MATERIALS A retrospective review of 100 consecutive GE studies at the University Hospital, San Antonio, Texas, was performed. Each patient received a semisolid meal containing corn flakes, milk, and sugar (200 kcal, 6 g fat, 7 g protein, and 30 g carbohydrates) and 37.0 MBq (1 mCi) of Tc-99m sulfur colloid according to a standard clinical protocol followed by dynamic 1-minute planar acquisitions for 60 minutes. Gastric emptying times were classified based on the 50% emptying time as follows: 30 to 60 minutes for normal, abnormally delayed as >60 minutes, and abnormally rapid as <30 minutes. RESULTS Twenty-eight patients demonstrated rapid GE, 25 delayed GE, and 45 normal GE. Fifteen (54%) patients with rapid GE were diabetic, 4 (14%) had impaired fasting glucose values, and 9 (32%) were normoglycemic. Fourteen (56%) patients with delayed GE were diabetic, one (4%) had impaired fasting glucose, and 10 (40%) were normoglycemic. Both patients with delayed and those with rapid GE had nausea as the most common symptom followed by early satiety (rapid GE) and vomiting (delayed GE). Of 28 patients with rapid GE, 26 were on promotility agents. CONCLUSION The number of patients with rapid GE of the corn flakes, milk, and sugar meal is appreciably greater (28%) than previously reported with other meals. This relative large number is likely related to the meal composition and the homogeneous dispersal of the label within the meal.
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Kuo P, Rayner CK, Jones KL, Horowitz M. Pathophysiology and management of diabetic gastropathy: a guide for endocrinologists. Drugs 2007; 67:1671-1687. [PMID: 17683169 DOI: 10.2165/00003495-200767120-00003] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Delayed gastric emptying is frequently observed in patients with long-standing type 1 and type 2 diabetes mellitus, and potentially impacts on upper gastrointestinal symptoms, glycaemic control, nutrition and oral drug absorption. The pathogenesis remains unclear and management strategies are currently suboptimal. Therapeutic strategies focus on accelerating gastric emptying, controlling symptoms and improving glycaemic control. The potential adverse effects of hyperglycaemia on gastric emptying and upper gut symptoms indicate the importance of normalising blood glucose if possible. Nutritional and psychological supports are also important, but often neglected. A number of recent pharmacological and non-pharmacological therapies show promise, including gastric electrical stimulation. As with all chronic illnesses, a multidisciplinary approach to management is recommended, but there are few data regarding long-term outcomes.
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Affiliation(s)
- Paul Kuo
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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Fear G, Komarnytsky S, Raskin I. Protease inhibitors and their peptidomimetic derivatives as potential drugs. Pharmacol Ther 2006; 113:354-68. [PMID: 17098288 PMCID: PMC7112583 DOI: 10.1016/j.pharmthera.2006.09.001] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2006] [Accepted: 09/05/2006] [Indexed: 01/28/2023]
Abstract
Precise spatial and temporal regulation of proteolytic activity is essential to human physiology. Modulation of protease activity with synthetic peptidomimetic inhibitors has proven to be clinically useful for treating human immunodeficiency virus (HIV) and hypertension and shows potential for medicinal application in cancer, obesity, cardiovascular, inflammatory, neurodegenerative diseases, and various infectious and parasitic diseases. Exploration of natural inhibitors and synthesis of peptidomimetic molecules has provided many promising compounds performing successfully in animal studies. Several protease inhibitors are undergoing further evaluation in human clinical trials. New research strategies are now focusing on the need for improved comprehension of protease-regulated cascades, along with precise selection of targets and improved inhibitor specificity. It remains to be seen which second generation agents will evolve into approved drugs or complementary therapies.
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Affiliation(s)
- Georgie Fear
- Biotech Center, Rutgers University, 59 Dudley Road, New Brunswick, NJ 08901, USA.
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20
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Chaikomin R, Rayner CK, Jones KL, Horowitz M. Upper gastrointestinal function and glycemic control in diabetes mellitus. World J Gastroenterol 2006; 12:5611-5621. [PMID: 17007012 PMCID: PMC4088160 DOI: 10.3748/wjg.v12.i35.5611] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/19/2006] [Revised: 06/06/2006] [Accepted: 06/16/2006] [Indexed: 02/06/2023] Open
Abstract
Recent evidence has highlighted the impact of glycemic control on the incidence and progression of diabetic micro- and macrovascular complications, and on cardiovascular risk in the non-diabetic population. Postprandial blood glucose concentrations make a major contribution to overall glycemic control, and are determined in part by upper gastrointestinal function. Conversely, poor glycemic control has an acute, reversible effect on gastrointestinal motility. Insights into the mechanisms by which the gut contributes to glycemia have given rise to a number of novel dietary and pharmacological strategies designed to lower postprandial blood glucose concentrations.
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Affiliation(s)
- Reawika Chaikomin
- Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
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Gentilcore D, Chaikomin R, Jones KL, Russo A, Feinle-Bisset C, Wishart JM, Rayner CK, Horowitz M. Effects of fat on gastric emptying of and the glycemic, insulin, and incretin responses to a carbohydrate meal in type 2 diabetes. J Clin Endocrinol Metab 2006; 91:2062-2067. [PMID: 16537685 DOI: 10.1210/jc.2005-2644] [Citation(s) in RCA: 243] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
CONTEXT Gastric emptying (GE) is a major determinant of postprandial glycemia. Because the presence of fat in the small intestine inhibits GE, ingestion of fat may attenuate the glycemic response to carbohydrate. OBJECTIVE The objective of this study was to evaluate the effect of patterns of fat consumption on GE and glucose, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) concentrations after a carbohydrate meal in type 2 diabetes. DESIGN This was a randomized, cross-over study in which GE of a radioisotopically labeled potato meal was measured on 3 d. SETTING The study was performed at the Royal Adelaide Hospital. PATIENTS Six males with type 2 diabetes were studied. INTERVENTION Subjects ingested 1) 30 ml water 30 min before the mashed potato (water), 2) 30 ml olive oil 30 min before the mashed potato (oil), or 3) 30 ml water 30 min before the mashed potato meal that contained 30 ml olive oil (water and oil). MAIN OUTCOME MEASURES GE, blood glucose, plasma insulin, GLP-1, and GIP concentrations were the main outcome measures. RESULTS GE was much slower with oil compared with both water (P < 0.0001) and water and oil (P < 0.05) and was slower after water and oil compared with water (P < 0.01). The postprandial rise in blood glucose was markedly delayed (P = 0.03), and peak glucose occurred later (P = 0.04) with oil compared with the two other meals. The rises in insulin and GIP were attenuated (P < 0.0001), whereas the GLP-1 response was greater (P = 0.0001), after oil. CONCLUSIONS Ingestion of fat before a carbohydrate meal markedly slows GE and attenuates the postprandial rises in glucose, insulin, and GIP, but stimulates GLP-1, in type 2 diabetes.
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Affiliation(s)
- Diana Gentilcore
- University of Adelaide, Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia
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Gentilcore D, Bryant B, Wishart JM, Morris HA, Horowitz M, Jones KL. Acarbose attenuates the hypotensive response to sucrose and slows gastric emptying in the elderly. Am J Med 2005; 118:1289. [PMID: 16271921 DOI: 10.1016/j.amjmed.2005.05.019] [Citation(s) in RCA: 62] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2004] [Accepted: 05/02/2005] [Indexed: 02/07/2023]
Affiliation(s)
- Diana Gentilcore
- University of Adelaide, Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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23
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Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O'Donovan D, Rayner CK, Horowitz M. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab 2005; 289:E504-E507. [PMID: 15886226 DOI: 10.1152/ajpendo.00099.2005] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The rate of gastric emptying of glucose-containing liquids is a major determinant of postprandial glycemia. The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Although overall emptying of glucose approximates 1-3 kcal/min, the "early phase" of gastric emptying is usually more rapid. We have evaluated the hypothesis that increased stimulation of incretin hormones and insulin by a more rapid initial rate of small intestinal glucose delivery would reduce the overall glycemic response to a standardized enteral glucose load. Twelve healthy subjects were studied on two separate days in which they received an intraduodenal (id) glucose infusion for 120 min. On one day, the infusion rate was variable, being more rapid (6 kcal/min) between t = 0 and 10 min and slower (0.55 kcal/min) between t = 10 and 120 min, whereas on the other day the rate was constant (1 kcal/min) from t = 0-120 min, i.e., on both days 120 kcal were given. Between t = 0 and 75 min, plasma insulin, GIP, and GLP-1 were higher with the variable infusion. Despite the increase in insulin and incretin hormones, blood glucose levels were also higher. Between t = 75 and 180 min, blood glucose and plasma insulin were lower with the variable infusion. There was no difference in the area under the curve 0-180 min for blood glucose. We conclude that stimulation of incretin hormone and insulin release by a more rapid initial rate of id glucose delivery does not lead to an overall reduction in glycemia in healthy subjects.
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Affiliation(s)
- Reawika Chaikomin
- Department Medicine, University of Adelaide, Royal Adelaide Hospital, North Terrace Adelaide, South Australia 5000, Australia
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Meier JJ, Kemmeries G, Holst JJ, Nauck MA. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects. Diabetes 2005; 54:2212-8. [PMID: 15983224 DOI: 10.2337/diabetes.54.7.2212] [Citation(s) in RCA: 99] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Glucagon-like peptide 1 (GLP-1) has been proposed to act as an incretin hormone due to its ability to enhance glucose-stimulated insulin secretion. Because GLP-1 also decelerates gastric emptying, it physiologically reduces rather than augments postprandial insulin secretory responses. Therefore, we aimed to antagonize the deceleration of gastric emptying by GLP-1 to study its effects on insulin secretion after a meal. Nine healthy male volunteers (age 25 +/- 4 years, BMI 25.0 +/- 4.9 kg/m2) were studied with an infusion of GLP-1 (0.8 pmol.kg(-1).min(-1) from -30 to 240 min) or placebo. On separate occasions, the prokinetic drugs metoclopramide (10 mg), domperidone (10 mg), cisapride (10 mg, all at -30 min per oral), or erythromycin (200 mg intravenously from -30 to -15 min) were administered in addition to GLP-1. A liquid test meal (50 g sucrose and 8% mixed amino acids in 400 ml) was administered at 0 min. Capillary and venous blood samples were drawn for the determination of glucose (glucose oxidase), insulin, C-peptide, GLP-1, glucagon, gastric inhibitory polypeptide (GIP), and pancreatic polypeptide (specific immunoassays). Gastric emptying was assessed by the phenol red dilution technique. Statistical analyses were performed using repeated-measures ANOVA and Duncan's post hoc test. GLP-1 significantly decelerated the velocity of gastric emptying (P < 0.001). This was completely counterbalanced by erythromycin, whereas the other prokinetic drugs used had no effect. Postprandial glucose concentrations were lowered by GLP-1 (P < 0.001 vs. placebo), but this effect was partially reversed by erythromycin (P < 0.05). Insulin secretory responses to the meal were lower during GLP-1 administration (P < 0.05 vs. placebo). However, when erythromycin was added to GLP-1, insulin concentrations were similar to those in placebo experiments. The suppression of meal-related increments in glucagon secretion by GLP-1 was reversed by erythromycin (P < 0.001). The time course of GIP secretion was delayed during GLP-1 administration (P < 0.05), but when erythromycin was added, the pattern was similar to placebo experiments. GLP-1 administration led to a reduction in pancreatic polypeptide plasma concentrations (P < 0.05). In contrast, pancreatic polypeptide levels were markedly increased by erythromycin (P < 0.001). Intravenous erythromycin counteracts the deceleration of gastric emptying caused by GLP-1, probably by interacting with the parasympathetic nervous system (pancreatic polypeptide responses). Despite augmented rises in insulin secretion, the glucose-lowering effect of GLP-1 is markedly reduced when the deceleration of gastric emptying is antagonized, illustrating the importance of this facet of the multiple antidiabetic actions of GLP-1.
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Affiliation(s)
- Juris J Meier
- Department of Medicine, Ruhr University, Bochum, Germany
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25
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O'Donovan D, Hausken T, Lei Y, Russo A, Keogh J, Horowitz M, Jones KL. Effect of aging on transpyloric flow, gastric emptying, and intragastric distribution in healthy humans--impact on glycemia. Dig Dis Sci 2005; 50:671-676. [PMID: 15844700 DOI: 10.1007/s10620-005-2555-3] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The aims of this study were to evaluate (i) the relationship between transpyloric flow (TF) assessed by Doppler ultrasonography and scintigraphy, (ii) the effects of healthy aging on TF and gastric emptying (GE), and (iii) the relationship between the glycemic response to oral glucose and TF. Ten healthy "young" (7 M, 3 F) and 8 "older" (4 M, 4 F), subjects had simultaneous measurements of TF, GE, and blood glucose after a 600-ml drink (75 g glucose labeled with 20 MBq 99mTc-sulfur colloid) while seated. TF measured by ultrasound was measured during drink ingestion and for 30 min thereafter. GE was measured scintigraphically for 180 min after drink ingestion. Blood glucose was measured before the drink and at regular intervals until 180 min. During drink ingestion, TF was greater (P < 0.05) and GE faster (retention at 60 min: 70.8+/-3.3 vs. 83.8+/-4.6%; P < 0.05) in young compared to older subjects. There was no difference in fasting blood glucose between the two groups but the magnitude of the rise in blood glucose was greater in the young compared to the older subjects; (at 15 min 2.4+/-0.3 vs. 1.5+/-0.5 mmol/L; P < 0.05). In contrast, after 90 min blood glucose concentrations were higher in the older subjects. There were significant relationships between the early blood glucose concentration and both TF (e.g., at 15 min: r = 0.56, P < 0.05) and GE (e.g., at 15 min: r = -0.51, P < 0.05). In conclusion, the results of this study indicate that (i) TF is initially less, and GE slower, in older compared to young subjects; (ii) the initial glycemic response to oral glucose is related to TF; and (iii) measurements of TF by ultrasound and scintigraphy correlate significantly.
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Affiliation(s)
- Deirdre O'Donovan
- Departments of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia
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Abstract
The gastrointestinal tract (GIT) is an interface between the external environment and the body and functions to extract nutrients from foods as well as handle the various non-nutrient compounds found in foods. Thus factors in foods that affect health and disease may mediate their effects either through a direct effect on the GIT or indirectly by the pattern of absorption and subsequent metabolism through the GIT. To explore this relationship one must consider both the physiological responses of the GIT induced by factors in foods as well as the implications of GIT adaptation for metabolism. Metabolic adaptations to dietary factors such as cholesterol levels, glucose and insulin response, and immune function appear to be modulated by the manner in which food factors are metabolized in the GIT. New research is needed to understand the inter-relationship between food factors that stimulate GIT response and the subsequent influence on metabolism that influences risk factors for disease and health promotion.
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Affiliation(s)
- Barbara Schneeman
- Department of Nutrition, University of California, One Shields Avenue, Davis, CA 95616, USA.
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Schneeman BO, Burton-Freeman B, Davis P. Incorporating Dairy Foods into Low and High Fat Diets Increases the Postprandial Cholecystokinin Response in Men and Women. J Nutr 2003; 133:4124-8. [PMID: 14652359 DOI: 10.1093/jn/133.12.4124] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
The postprandial period is a dynamic state of hormone and lipoprotein metabolism that can be influenced by dietary composition. The objective of this study was to determine whether the source of dietary fat [dairy (D) vs. nondairy (ND)] would modify the lipemic, insulin and cholecystokinin (CCK) response to high or low fat meals. Men and women (n = 24) consumed 4 test meals with a similar polyunsaturated:saturated (P:S; 0.12:1) fat ratio. The diets were high (38% energy) or low (20% energy) in fat, with or without fat from dairy sources. CCK responses were greater after consumption of meals containing D than ND, and for high compared with low fat meals. Women had higher CCK responses than men and were more sensitive to the differences in dietary treatments. Consumption of low fat meals resulted in greater insulin responses than high fat meals. However, after consumption of the low fat meals, the insulin response of D was about half of the ND response; no differences in insulin response were detected after the high fat meals. Triacylglyceride response was influenced primarily by the fat content of the diet. Consumption of dairy products containing fat was associated with an enhanced CCK response, which may have implications for the regulation of food intake. Blunting glucose and insulin response in low fat meals containing fat from dairy products may be useful for glycemic control.
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Affiliation(s)
- Barbara O Schneeman
- Department of Nutrition, University of California-Davis, Davis, CA 95616, USA.
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Abstract
The management of diabetic gastroparesis often represents a significant clinical challenge in which the maintenance of nutrition is pivotal. Gastric emptying is delayed in 30% to 50% of patients with longstanding type 1 or type 2 diabetes and upper gastrointestinal symptoms also occur frequently. However, there is only a weak association between the presence of symptoms and delayed gastric emptying. Acute changes in blood glucose concentrations affect gastric motility in diabetes; hyperglycemia slows gastric emptying whereas hypoglycemia may accelerate it; blood glucose concentrations may also influence symptoms. It is now recognized that gastric emptying is a major determinant of postprandial glycemia and, therefore, there is considerable interest in the concept of modulating gastric emptying, by dietary or pharmacologic means, to optimize glycemic control in diabetes.
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Affiliation(s)
- Diana Gentilcore
- Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia 5000, Australia.
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Abstract
While the health benefit of a functional food may be a metabolic response that lowers risk for disease, the actual target for the food or food component may be on the functioning of the gastrointestinal tract (GIT). For example, slowing absorption from the intestine, as measured by examining the appearance of the nutrient or food component in the blood, the hormone response associated with absorption of the compound or excretion of the compound, may provide a health benefit. However, the food component may slow absorption by delaying gastric emptying, altering the mixing within the intestinal contents or decreasing the availability of digestive enzymes in the intestine. These measures of GIT function provide validation of the mechanisms by which the functional food or food components affect metabolism. Bioavailability of physiologically active compounds from foods will be determined by the digestibility of foods that contain these compounds, their subsequent absorption and utilization by tissues. The physical structure of foods contributes to the functional effects of foods as well as to the availability of compounds from foods. For example, recent studies have demonstrated that changing the viscosity of the gut contents alters absorption and GIT response. Additionally, food structures such as the plant cell wall change the availability of absorbable compounds along the gastrointestinal contents. The areas of probiotics and prebiotics have highlighted the potential importance of gut microflora in health. While evidence suggests biological activity relevant to disease risk reduction, the long-term implications of the microbial activity have yet to be established.
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Blat S, Guérin S, Chauvin A, Sève B, Morgan L, Cuber JC, Malbert CH. The vagus is inhibitory of the late postprandial insulin secretion in conscious pigs. Auton Neurosci 2002; 101:68-77. [PMID: 12462361 DOI: 10.1016/s1566-0702(02)00184-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The vagus is involved in the cephalic phase of insulin secretion but its role in the meal absorption phase of insulin release remains to be defined. The aim of this study was therefore to evaluate the role of the vagus in the early and the late meal absorption phases of insulin secretion. In six pigs, venous insulin profiles were compared in intact animals, after ventral or dorsal vagal trunk section, and after section of both vagal trunks (truncal vagotomy). Since gastric emptying could be modified by vagotomy, it was recorded concomitantly by gamma scintigraphy. Semi-solid (porridge) and liquid (glucose 10%) meals were tested. Truncal vagotomy significantly increased insulin release compare to intact animals after glucose (63.8%) and porridge (174.4%) meals in the early and the late absorption phases of insulin secretion, respectively. For the glucose meal, this effect could be explained by a vagally mediated change in gastric emptying rate, since insulin concentrations for a similar amount of nutrient propelled to the duodenum were not different in intact and truncal vagotomized animals. In contrast, after the porridge meal, truncal vagotomy was associated with a second, later occurring increase in circulating insulin, which could not be explained by changes in gastric emptying rate. These results demonstrate for the first time an inhibitory role of the vagus in the late meal absorption phase of insulin release.
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Burton-Freeman B, Davis PA, Schneeman BO. Plasma cholecystokinin is associated with subjective measures of satiety in women. Am J Clin Nutr 2002; 76:659-67. [PMID: 12198015 DOI: 10.1093/ajcn/76.3.659] [Citation(s) in RCA: 69] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Cholecystokinin is associated with satiety. Fat stimulates cholecystokinin release, and fiber appears to prolong cholecystokinin elevation during the alimentary period. OBJECTIVE We tested whether adding fiber or fat to a low-fat, low-fiber meal increases cholecystokinin release and enhances subjective measures of satiety and whether the cholecystokinin response correlates with subjective measures of satiety. DESIGN Three isoenergetic breakfast meals were tested in a randomized crossover design: low fiber, low fat; high fiber, low fat; and low fiber, high fat. Blood samples were drawn from fasted subjects (7 men and 8 women) before and at different time points after test meal consumption for 6 h. Plasma was analyzed for cholecystokinin, insulin, glucose, and triacylglycerols. Visual analogue scales were used to assess subjects' hunger, desire to eat, fullness, and prospective consumption. RESULTS In the women, the meals higher in fiber or in fat resulted in greater feelings of satiety and in significantly higher cholecystokinin responses than did the low-fat, low-fiber meal. In the men, the increase in cholecystokinin concentration did not differ between meals, but the 2 low-fat meals elicited a greater feeling of satiety than did the high-fat meal. The insulin response was significantly higher for the low-fiber, low-fat meal than for the other 2 meals, and the triacylglycerol response was greatest for the high-fat, low-fiber meal. CONCLUSION In women, the feeling of satiety caused by cholecystokinin release is enhanced by increasing either the fiber or fat content of a low-fat, low-fiber meal.
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Affiliation(s)
- Britt Burton-Freeman
- Department of Nutrition and the Division of Endocrinology, Clinical Nutrition, and Vascular Medicine, University of California, Davis 95616, USA
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Horowitz M, O'Donovan D, Jones KL, Feinle C, Rayner CK, Samsom M. Gastric emptying in diabetes: clinical significance and treatment. Diabet Med 2002; 19:177-194. [PMID: 11918620 DOI: 10.1046/j.1464-5491.2002.00658.x] [Citation(s) in RCA: 203] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.
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Affiliation(s)
- M Horowitz
- Department of Medicine, University of Adelaide, Adelaide, South Australia.
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Bourdon I, Olson B, Backus R, Richter BD, Davis PA, Schneeman BO. Beans, as a source of dietary fiber, increase cholecystokinin and apolipoprotein b48 response to test meals in men. J Nutr 2001; 131:1485-90. [PMID: 11340104 DOI: 10.1093/jn/131.5.1485] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Dry beans lower plasma cholesterol, an effect that has been associated with both the fiber and the protein content of beans. The objective of this study was to determine the acute hormone and lipid responses to a test meal that contained dry beans as a source of dietary fiber. A crossover design was employed in which men consumed the test meal and a control meal in random order. Both meals contained egg, bread, jelly, orange juice, milk and margarine. The high fiber meal contained white beans, whereas the low fiber (control) meal contained rice and dry milk. The men maintained their normal dietary pattern and fasted overnight before the study days. After a fasting blood sample was drawn, the men consumed the test meal and blood samples were collected over the next 6 h. Blood samples were analyzed for cholecystokinin (CCK), insulin and glucose. Plasma was separated into lipoprotein fractions and the triglyceride, cholesterol, apolipoprotein (apo) B100 and B48 content of triglyceride-rich lipoproteins determined. Insulin and glucose responses did not differ significantly between test meals; however, the CCK response was twice as high after the bean-containing meal than after the low fiber meal (P = 0.03). The increase in apo B48 concentration was significantly higher after the bean meal than after the low fiber meal (P < 0.05). Adding beans to a meal to increase fiber content prolongs the postprandial presence of intestinally derived lipoproteins and augments the CCK response to the meal.
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Affiliation(s)
- I Bourdon
- Department of Nutrition, School of Veterinary Medicine, University of California, Davis, CA 95616, USA
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Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care 2001; 24:371-381. [PMID: 11213895 DOI: 10.2337/diacare.24.2.371] [Citation(s) in RCA: 305] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.
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Affiliation(s)
- C K Rayner
- University of Adelaide Department of Medicine, Royal Adelaide Hospital, South Australia, Australia
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Kral JG, Buckley MC, Kissileff HR, Schaffner F. Metabolic correlates of eating behavior in severe obesity. Int J Obes (Lond) 2001; 25:258-64. [PMID: 11410829 DOI: 10.1038/sj.ijo.0801469] [Citation(s) in RCA: 63] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/1999] [Revised: 06/20/2000] [Accepted: 08/07/2000] [Indexed: 11/09/2022]
Abstract
BACKGROUND The benefit of spreading energy intake over many small meals ('nibbling') rather than few large ones ('gorging') for control of blood glucose, serum lipids and body fat accretion has been known for 60 y, but the mechanisms are poorly understood. Men exhibit more of a gorging eating pattern than women and are also more prone to the metabolic complications of obesity, as are women with a 'male', central distribution of adipose tissue. We have shown correlations between central fat distribution, and other components of the metabolic 'Syndrome X' and fatty infiltration of the liver. Here we study relationships between eating rate and fat distribution and test the hypothesis that gorging might be associated with fatty liver. SUBJECTS AND METHODS In 30 non-alcoholic, non-diabetic, severely obese women (body mass index, BMI=47+/-1 kg/m(2); mean+/-s.e.m.) with a mean age of 36+/-1 y and 16 men (BMI: 52+/-3) age 38+/-2 y, who were candidates for anti-obesity surgery, we measured eating rate using an eating monitor, and fat distribution by the waist-hip circumference ratio (WHR). In addition in the 17 women and 11 men who had surgery, serum lipids were analyzed and routine liver biopsies were evaluated for steatosis by a pathologist blinded to the conditions of the study. RESULTS Men ate significantly faster than women (188+/-28 vs 123+/-9 g/min; P<0.01), and had more liver fat (score: 2.7+/-03 vs 1.5+/-0.3; P<0.01), with no statistically significant sex differences in s-cholesterol or s-triglycerides. Eating rate correlated with WHR (r=0.46; P<0.01, n=46), liver fat (r=0.55; P<0.01), and s-triglycerides (r=0.42; P<0.05) adjusting for sex. Liver fat correlated with WHR (r=0.50; P<0.05), s-triglycerides (r=0.70; P<0.01) and s-cholesterol (r=0.50; P<0.05), while there were no significant correlations with BMI or body weight. In multivariate analysis eating rate (32%), meal size (8%) and WHR (6%) contributed 46% of the variance in liver fat. CONCLUSION We showed increased eating rates in severely obese men and women with central fat distribution. Furthermore, increased eating rates were associated with fatty liver and elevated serum lipids. Eating rate in severely obese women and men may be a determinant of the metabolic syndrome.
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Affiliation(s)
- J G Kral
- Department of Surgery, SUNY HSC at Brooklyn, New York 11203-2098, USA
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Kong MF, Horowitz M. Gastric emptying in diabetes mellitus: relationship to blood-glucose control. Clin Geriatr Med 1999; 15:321-338. [PMID: 10339636 DOI: 10.1016/s0749-0690(18)30062-4] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The application of novel investigative techniques has established that disordered gastric motility is a frequent complication of diabetes mellitus. Thus, gastric emptying of solid or nutrient liquid meals is abnormal in 30% to 50% of randomly selected outpatients with long-standing type 1 or type 2 diabetes. Delayed gastric emptying occurs more frequently than rapid emptying. There is increasing evidence that disordered gastric motility has a major impact on the management of patients with diabetes mellitus by leading to gastrointestinal symptoms and poor glycemic control. Although both gastroparesis and upper gastrointestinal symptoms have been attributed to irreversible autonomic damage, it is now clear that acute changes in the blood-glucose concentration have a major effect on both gastrointestinal motor function and the perception of sensations arising in the gut. For example, there is an inverse relationship between the rate of gastric emptying and the blood-glucose concentration, so that gastric emptying is slower during hyperglycemia and accelerated during hypoglycemia. This article reviews some issues in the etiology, diagnosis, and management of problems associated with gastric emptying in elderly persons with diabetes mellitus.
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Affiliation(s)
- M F Kong
- Department of Medicine, Royal Adelaide Hospital, North Terrace, Adelaide, Australia
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Horowitz M, Rayner C, Kong MF, Jones KL, Wishart JM, Sun WM, Fraser R. Gastrointestinal motor function in diabetes mellitus: Relationship to blood glucose concentrations. J Gastroenterol Hepatol 1998; 13:S239-S245. [PMID: 28976661 DOI: 10.1111/j.1440-1746.1998.tb01885.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
The application of novel investigative techniques has established that there is a high prevalence of disordered gastrointestinal motor function in patients with diabetes mellitus and has provided insights into its pathogenesis and clinical significance. Acute changes in the blood glucose concentration, even within the normal postprandial range, affect both gastrointestinal motor function and the perception of sensations arising from the gastrointestinal tract. Gastric emptying is slower during hyperglycaemia and accelerated during hypoglycaemia; the perception of gastric distension is greater during hyperglycaemia than euglycaemia. The pathways mediating the effects of the blood glucose concentration on gut motility and sensation are poorly defined. The rate of gastric emptying is an important determinant of postprandial blood glucose concentrations and there is increasing evidence that gastric emptying can be modulated therapeutically in order to optimize glycaemic control in patients with diabetes.
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Affiliation(s)
- Michael Horowitz
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Chris Rayner
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Marie-France Kong
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Karen L Jones
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Judith M Wishart
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Wei-Ming Sun
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
| | - Robert Fraser
- Department of Medicine, Royal Adelaide Hospital, Adelaide, South Australia, Australia
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