scholarly journals The effect of 8 days of strict bed rest on the incretin effect in healthy volunteers

2016 ◽  
Vol 120 (6) ◽  
pp. 608-614 ◽  
Author(s):  
Signe Tellerup Nielsen ◽  
Nina Majlund Harder-Lauridsen ◽  
Fabiana Braga Benatti ◽  
Anne-Sophie Wedell-Neergaard ◽  
Mark Preben Lyngbæk ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Physical Inactivity ◽  
Insulin Response ◽  
Bed Rest ◽  
Fat Free Mass ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Intravenous Glucose ◽  
C Peptide

Bed rest and physical inactivity are the consequences of hospital admission for many patients. Physical inactivity induces changes in glucose metabolism, but its effect on the incretin effect, which is reduced in, e.g., Type 2 diabetes, is unknown. To investigate how 8 days of strict bed rest affects the incretin effect, 10 healthy nonobese male volunteers underwent 8 days of strict bed rest. Before and after the intervention, all volunteers underwent an oral glucose tolerance test (OGTT) followed by an intravenous glucose infusion (IVGI) on the following day to mimic the blood glucose profile from the OGTT. Blood glucose, serum insulin, serum C-peptide, plasma incretin hormones [glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP)], and serum glucagon were measured serially during both the OGTT and the IVGI. The incretin effect is calculated as the relative difference between the area under the curve for the insulin response during the OGTT and that of the corresponding IVGI, respectively. Concentrations of glucose, insulin, C-peptide, and GIP measured during the OGTT were higher after the bed rest intervention (all P < 0.05), whereas there was no difference in the levels of GLP-1 and Glucagon. Bed rest led to a mean loss of 2.4 kg of fat-free mass, and induced insulin resistance evaluated by the Matsuda index, but did not affect the incretin effect ( P = 0.6). In conclusion, 8 days of bed rest induces insulin resistance, but we did not see evidence of an associated change in the incretin effect.

scholarly journals The Incretin Effect in Female Mice With Double Deletion of GLP-1 and GIP Receptors

2019 ◽  
Vol 4 (2) ◽  
Author(s):  
Bo Ahrén ◽  
Yuichiro Yamada ◽  
Yutaka Seino
Keyword(s):  
Insulin Secretion ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Insulin Response ◽  
Oral Glucose ◽  
Incretin Effect ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Female Mice

Abstract To establish the contribution of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) for the incretin effect after oral glucose, studies were undertaken in female mice with genetic deletion of receptors for GIP and GLP-1 (double incretin receptor knockout [DIRKO] mice) and their wild-type (WT) counterparts. Insulin secretion was explored after oral glucose (doses ranging from 0 to 100 mg), after intravenous glucose (doses ranging from 0 to 0.75 g/kg), and after oral and intravenous glucose at matching circulating glucose. DIRKO mice had glucose intolerance after oral glucose challenges in association with impaired beta-cell function. Suprabasal area under the curve for C-peptide (AUCC-peptide) correlated linearly with suprabasal AUCglucose both in WT (r = 0.942, P = .017) and DIRKO mice (r = 0.972, P = .006). The slope of this regression was lower in DIRKO than in WT mice (0.012 ± 0.006 vs 0.031 ± 0.006 nmol C-peptide/mmol glucose, P = .042). In contrast, there was no difference in the insulin response to intravenous glucose between WT and DIRKO mice. Furthermore, oral and intravenous glucose administration at matching glucose levels showed that the augmentation of insulin secretion after oral glucose (the incretin effect) in WT mice (11.8 ± 2.3 nmol/L min) was entirely absent in DIRKO mice (3.3 ± 1.2 nmol/L min). We conclude that GIP and GLP-1 are required for normal glucose tolerance and beta-cell function after oral glucose in mice, that they are the sole incretin hormones after oral glucose at higher dose levels, and that they contribute by 65% to insulin secretion after oral glucose.

scholarly journals OR23-06 Is the Improved Glucose Homeostasis in Patients with Acromegaly Treated with Pegvisomant Caused by Improved Glucagon Secretion?

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Nanna Thurmann Jørgensen, miss ◽  
Trine Møller Erichsen ◽  
Marianne C Klose ◽  
Morten Buus Jørgensen ◽  
Thomas Idorn ◽  
...  
Keyword(s):  
Glucose Homeostasis ◽  
Insulin Response ◽  
Glucagon Secretion ◽  
Somatostatin Analogues ◽  
Favorable Effect ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Incretin Effect ◽  
Intravenous Glucose

Abstract Context: Active acromegaly is associated with impaired glucose metabolism, which improves upon treatment. Treatment with first generation somatostatin analogues (SSA) has a detrimental effect on insulin secretion, but the effect on glucose homeostasis is neutralized by the reduction in growth hormone (GH) and Insulin-like growth factor-1 (IGF-1). Treatment with GH receptor antagonists has a more favorable effect on glucose homeostasis. Objective: To describe the secretion of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP1), and glucose-dependent insulinotropic polypeptide (GIP) in surgically treated patients with acromegaly treated or not with somatostatin analogues, either as monotherapy (SSA) or in co-treatment with pegvisomant (SSA+PEG), respectively, compared to healthy controls. Methods: Descriptive study of data from 23 surgically treated, non-diabetic patients with acromegaly and 6 healthy controls. After an overnight fast, all participants underwent a three-hour 75 g oral glucose tolerance test (OGTT) and subsequently a three-hour isoglycaemic intravenous glucose infusion on a separate day. Analysis: Baseline hormone concentrations, time to peak and area under the curve (AUC) on the OGTT-day, and the incretin effect in the patient groups and controls were compared using analysis of variance with post-hoc analysis. Results: The total group of patients treated with somatostatin analogues (N=15) had numerically impaired glucose, insulin, GLP1 and glucagon responses (AUC, P&gt;0.05 respectively), and an impaired GIP-response (AUC, P=0.007) during OGTT as compared to patients not treated with somatostatin analogues and healthy controls. Similarly, the incretin effect was numerically impaired. Patients co-treated with pegvisomant (SSA+PEG, N=4) had a numerically increased secretion of insulin and glucagon compared to patients on SSA (N=11) during OGTT (insulin AUC mean (SEM), SSA+PEG 49 nmol/l*min (8.3) vs SSA 25 (3.4), P&gt;0.05) [healthy controls 62 (13.6)]; glucagon AUC, SSA+PEG 823 pmol/l*min (194) vs SSA 332 (69), P&gt;0.05) [healthy controls 946 (233)]). GIP secretion remained significantly impaired, whereas GLP1 secretion was numerically increased with PEG (SSA+PEG 3088 pmol/l*min (366) vs SSA 2401 (239), P&gt;0.05) [healthy controls 3972 (451)] but remained without a glucose-dependant increase as in SSA. The incretin effect numerically increased in SSA+PEG compared to SSA (SSA+PEG 49.9% (13.9) vs SSA 33.6% (47.4), P&gt;0.05) [healthy controls 55.5% (7.7)]. Conclusion: Somatostatin analogues impaired the secretion of both insulin, glucagon and incretin hormones secretion. Co-treatment with pegvisomant seemed to counteract the somatostatinergic inhibition of the glucagon secretion and improved the insulin response to OGTT. We speculate that pegvisomant exerts its action via GH-receptors on pancreatic δ-cells.

scholarly journals The augmenting effect on insulin secretion by oral versus intravenous glucose is exaggerated by high-fat diet in mice

2008 ◽  
Vol 197 (1) ◽  
pp. 181-187 ◽  
Author(s):  
Bo Ahrén ◽  
Maria Sörhede Winzell ◽  
Giovanni Pacini
Keyword(s):  
Insulin Secretion ◽  
High Fat Diet ◽  
Insulin Response ◽  
Area Under The Curve ◽  
Oral Glucose ◽  
Incretin Effect ◽  
High Fat ◽  
Intravenous Glucose ◽  
Insulin Resistant ◽  
Glucose Levels

To study whether the incretin effect is involved in adaptively increased insulin secretion in insulin resistance, glucose was infused at a variable rate to match glucose levels after oral glucose (25 mg) in normal anesthetized C57BL/6J female mice or in mice rendered insulin resistant by 8 weeks of high-fat feeding. Insulin response was markedly higher after oral than i.v. glucose in both groups, and this augmentation was even higher in high-fat fed than normal mice. In normal mice, the area under the curve (AUCinsulin) was augmented from 4.0±0.8 to 8.0±1.8 nmol/l×60 min by the oral glucose, i.e. by a factor of 2 (P=0.023), whereas in the high-fat fed mice, AUCinsulin was augmented from 0.70±0.4 to 12.4±2.5 nmol/l×60 min, i.e. by a factor of 17 (P<0.001). To examine whether the incretin hormone glucagon-like peptide-1 (GLP-1) is responsible for this difference, the effect of i.v. GLP-1 was compared in normal and high-fat fed mice. The sensitivity to i.v. GLP-1 in stimulating insulin secretion was increased in the high-fat diet fed mice: the lowest effective dose of GLP-1 was 650 pmol/kg in normal mice and 13 pmol/kg in the high-fat diet fed mice. We conclude that 1) the incretin effect contributes by ∼50% to insulin secretion by the oral glucose in normal mice, 2) this effect is markedly exaggerated in insulin-resistant mice fed a high-fat diet, and 3) this augmented incretin contribution in the high-fat fed mice may partially be explained by GLP-1.

scholarly journals The T Allele of TCF7L2 Rs7903146 Predicts Increased Blood Glucose After Seven Days of Bed Rest in Nondiabetic Older Adults in a Secondary Analysis of a Randomized Controlled Trial

2021 ◽  
Author(s):  
Jean L. Fry ◽  
Katherine L. Thompson ◽  
Christopher S. Fry ◽  
Douglas Paddon-Jones ◽  
Emily J. Arentson-Lantz
Keyword(s):  
Older Adults ◽  
Blood Glucose ◽  
Physical Inactivity ◽  
Controlled Trial ◽  
Fasting Blood Glucose ◽  
Bed Rest ◽  
Oral Glucose ◽  
Common Genetic Variants ◽  
Increased Risk ◽  
Tcf7l2 Rs7903146

Abstract Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model is a simulated hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) and included a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted elevated 2-hour OGTT blood glucose (p = 0.03925). We show that the TCF7L2 rs7903146 T allele confers risk for elevated 2-hour OGTT blood glucose in nondiabetic older adults following 7 days of bed rest.

Effect of 10 days of physical inactivity on glucose tolerance in master athletes

1990 ◽  
Vol 68 (5) ◽  
pp. 1833-1837 ◽  
Author(s):  
M. A. Rogers ◽  
D. S. King ◽  
J. M. Hagberg ◽  
A. A. Ehsani ◽  
J. O. Holloszy
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
Plasma Glucose ◽  
Physical Inactivity ◽  
Insulin Response ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Master Athletes ◽  
Short Term ◽  
Glucose Response

Master athletes who exercise regularly appear to avoid the development of insulin resistance and deterioration of glucose tolerance (GT) commonly seen with aging. To evaluate the possibility that exercise prevents rather than masks the aging-related changes responsible for development of insulin resistance, we investigated the effects of 10 days of physical inactivity in 14 master athletes aged 61 +/- 2 (SE) yr. The response of 10 of these men to inactivity was similar to that of young athletes, with an unchanged plasma glucose response and a significantly greater insulin response to an oral glucose tolerance test (OGTT) after 10 days of inactivity. These 10 athletes appeared to have been protected against the aging-related changes in GT because their plasma glucose and insulin levels during the OGTT after 10 days of inactivity were not significantly different from those of young lean sedentary men. In contrast, a deterioration in GT occurred in four of the master athletes during 10 days of inactivity; this was sufficiently marked in two of them to be classified as impaired GT. We conclude that regular exercise may 1) protect against the development of insulin resistance and decline in GT with aging in individuals with normal GT and 2) normalize GT by means of short-term effects of exercise in some individuals with abnormal GT.

scholarly journals Metabolomics analysis reveals altered metabolites in lean compared with obese adolescents and additional metabolic shifts associated with hyperinsulinaemia and insulin resistance in obese adolescents: a cross-sectional study

Metabolomics ◽  
2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Elisabeth Müllner ◽  
Hanna E. Röhnisch ◽  
Claudia von Brömssen ◽  
Ali A. Moazzami
Keyword(s):  
Insulin Resistance ◽  
Amino Acids ◽  
Glucose Tolerance ◽  
Insulin Response ◽  
Oral Glucose ◽  
Response Level ◽  
Metabolic Alterations ◽  
Obese Adolescents ◽  
Branched Chain ◽  
Metabolomics Analysis

Abstract Introduction Hyperinsulinaemia and insulin resistance (IR) are strongly associated with obesity and are forerunners of type 2 diabetes. Little is known about metabolic alterations separately associated with obesity, hyperinsulinaemia/IR and impaired glucose tolerance (IGT) in adolescents. Objectives To identify metabolic alterations associated with obesity, hyperinsulinaemia/IR and hyperinsulinaemia/IR combined with IGT in obese adolescents. Methods 81 adolescents were stratified into four groups based on body mass index (lean vs. obese), insulin responses (normal insulin (NI) vs. high insulin (HI)) and glucose responses (normal glucose tolerance (NGT) vs. IGT) after an oral glucose tolerance test (OGTT). The groups comprised: (1) healthy lean with NI and NGT, (2) obese with NI and NGT, (3) obese with HI and NGT, and (4) obese with HI and IGT. Targeted nuclear magnetic resonance-based metabolomics analysis was performed on fasting and seven post-OGTT plasma samples, followed by univariate and multivariate statistical analyses. Results Two groups of metabolites were identified: (1) Metabolites associated with insulin response level: adolescents with HI (groups 3–4) had higher concentrations of branched-chain amino acids and tyrosine, and lower concentrations of serine, glycine, myo-inositol and dimethylsulfone, than adolescents with NI (groups 1–2). (2) Metabolites associated with obesity status: obese adolescents (groups 2–4) had higher concentrations of acetylcarnitine, alanine, pyruvate and glutamate, and lower concentrations of acetate, than lean adolescents (group 1). Conclusions Obesity is associated with shifts in fat and energy metabolism. Hyperinsulinaemia/IR in obese adolescents is also associated with increased branched-chain and aromatic amino acids.

Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium

2021 ◽  
Author(s):  
Ying Zhao ◽  
Yan Shu ◽  
Ning Zhao ◽  
Zili Zhou ◽  
Xiong Jia ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Circadian Rhythm ◽  
Blood Glucose ◽  
Glucose Metabolism ◽  
Sleep Deprivation ◽  
Rhesus Macaques ◽  
Intravenous Glucose ◽  
Increased Risk ◽  
The Impact

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.

Development of hyperinsulinemia and insulin resistance during the early stage of weight gain

2008 ◽  
Vol 294 (3) ◽  
pp. E568-E575 ◽  
Author(s):  
Johannes Erdmann ◽  
Bianca Kallabis ◽  
Ulrich Oppel ◽  
Oleg Sypchenko ◽  
Stefan Wagenpfeil ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Weight Gain ◽  
Early Stage ◽  
Normal Range ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Glucose Levels ◽  
Hyperglycemic Clamp ◽  
First Time

Obesity is associated with insulin resistance and hyperinsulinemia, which is considered to be a core component in the pathophysiology of obesity-related comorbidities. As yet it is unknown whether insulin resistance and hyperinsulinemia already develop during weight gain within the normal range. In 10 healthy male subjects the effect of intentional weight gain by 2 BMI points was examined on insulin. C-peptide and glucose levels following a meal, 75 g of glucose, and a two-step hyperglycemic clamp increased plasma glucose by 1.38 and 2.75 mmol/l, respectively. Baseline insulin, C-peptide, and glucose concentrations were significantly higher after weight gain from 21.8 to 23.8 kg/m2 BMI within 41/2 mo. Calculations of insulin secretion and clearance indicate that reduced insulin clearance contributes more to post-weight gain basal hyperinsulinemia than insulin secretion. Following oral or intravenous stimulation insulin concentrations were significantly higher post-weight gain during all three test conditions, whereas C-peptide and glucose levels did not differ. Calculations of insulin secretion and clearance demonstrated that higher stimulated insulin concentrations are entirely due to clearance but not secretion. Despite significantly higher insulin levels, the rate of intravenous glucose required to maintain the defined elevation of glucose levels was either identical (1.38 mmol/l) or even significantly lower (2.75 mmol/l) following weight gain. The present study demonstrates for the first time that insulin resistance already develops during weight gain within the normal range of body weight. The associated basal and stimulated hyperinsulinemia is the result of differentiated changes of insulin secretion and clearance, respectively.

scholarly journals Experimental BPA Exposure and Glucose-Stimulated Insulin Response in Adult Men and Women

2018 ◽  
Vol 2 (10) ◽  
pp. 1173-1187 ◽  
Author(s):  
Richard W Stahlhut ◽  
John Peterson Myers ◽  
Julia A Taylor ◽  
Angel Nadal ◽  
Jonathan A Dyer ◽  
...  
Keyword(s):  
Environmental Protection Agency ◽  
Metabolic Diseases ◽  
Insulin Response ◽  
Percentage Change ◽  
Oral Glucose ◽  
Insulinogenic Index ◽  
Strong Positive Correlation ◽  
Control Session ◽  
Cross Sectional ◽  
C Peptide

Abstract Context Human cross-sectional and animal studies have shown an association of the chemical bisphenol A (BPA) with insulin resistance, type 2 diabetes, and other metabolic diseases, but no human experimental study has investigated whether BPA alters insulin/C-peptide secretion. Design Men and postmenopausal women (without diabetes) were orally administered either the vehicle or a BPA dose of 50 µg/kg body weight, which has been predicted by US regulators (Food and Drug Administration, Environmental Protection Agency) to be the maximum, safe daily oral BPA dose over the lifetime. Insulin response was assessed in two cross-over experiments using an oral glucose tolerance test (OGTT; experiment 1) and a hyperglycemic (HG) clamp (experiment 2). Main outcomes were the percentage change of BPA session measures relative to those of the control session. Results Serum bioactive BPA after experimental exposure was at levels detected in human biomonitoring studies. In the OGTT, a strong positive correlation was found between hemoglobin A1c(HbA1c) and the percentage change in the insulinogenic index (Spearman = 0.92), an indicator of early-phase insulin response, and the equivalent C-peptide index (Pearson = 0.97). In the HG clamp study, focusing on the later-phase insulin response to a stable level of glucose, several measures of insulin and C-peptide appeared suppressed during the BPA session relative to the control session; the change in insulin maximum concentration (Cmax) was negatively correlated with HbA1c and the Cmax of bioactive serum BPA. Conclusions This exploratory study suggests that BPA exposure to a dose considered safe by US regulators may alter glucose-stimulated insulin response in humans.

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