scholarly journals Overnight hypoxic exposure and glucagon-like peptide-1 and leptin levels in humans

2008 ◽  
Vol 33 (5) ◽  
pp. 929-935 ◽  
Author(s):  
Eric M. Snyder ◽  
Richard D. Carr ◽  
Carolyn F. Deacon ◽  
Bruce D. Johnson
Keyword(s):  
Normobaric Hypoxia ◽  
Hypoxic Exposure ◽  
Healthy Humans ◽  
Endocrine Factors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Fraction Of Inspired Oxygen ◽  
Loss Of Appetite ◽  
Plasma Leptin ◽  
Inspired Oxygen

Altitude exposure has been associated with loss of appetite and weight loss in healthy humans; however, the endocrine factors that contribute to these changes remain unclear. Leptin and glucagon-like peptide-1 (GLP-1) are peptide hormones that contribute to the regulation of appetite. Leptin increases with hypoxia; however, the influence of hypoxia on GLP-1 has not been studied in animals or humans to date. We sought to determine the influence of normobaric hypoxia on plasma leptin and GLP-1 levels in 25 healthy humans. Subjects ingested a control meal during normoxia and after 17 h of exposure to normobaric hypoxia (fraction of inspired oxygen of 12.5%, simulating approximately 4100 m). Plasma leptin was assessed before the meal, and GLP-1 was assessed premeal, at 20 min postmeal, and at 40 min postmeal. We found that hypoxia caused a significant elevation in plasma leptin levels (normoxia, 4.9 ± 0.8 pg·mL–1; hypoxia, 7.7 ± 1.5 pg·mL–1; p < 0.05; range, –16% to 190%), no change in the average GLP-1 response to hypoxia, and only a small trend toward an increase in GLP-1 levels 40 min postmeal (fasting, 15.7 ± 0.9 vs 15.9 ± 0.7 pmol·L–1; 20 min postmeal, 21.7 ± 0.9 vs 21.8 ± 1.2 pmol·L–1; 40 min postmeal, 19.5 ± 1.2 vs. 21.0 ± 1.2 pmol·L–1 for normoxia and hypoxia, respectively; p > 0.05 normoxia vs hypoxia). There was a correlation between SaO2 and leptin after the 17 h exposure (r = 0.45; p < 0.05), but no relation between SaO2 and GLP-1. These data confirm that leptin increases with hypoxic exposure in humans. Further study is needed to determine the influence of hypoxia and altitude on GLP-1 levels.

A liquid mixed meal or exogenous glucagon-like peptide 1 (GLP-1) do not alter plasma leptin concentrations in healthy volunteers

1997 ◽  
Vol 34 (3) ◽  
pp. 230-234 ◽  
Author(s):  
C. Drewes ◽  
M. A. Nauck ◽  
R. Horn ◽  
J. Holst ◽  
W. Schmiegel ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Mixed Meal ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Plasma Leptin

Effects of rectal administration of taurocholic acid on glucagon-like peptide-1 and peptide YY secretion in healthy humans

2012 ◽  
Vol 15 (5) ◽  
pp. 474-477 ◽  
Author(s):  
T. Wu ◽  
M. J. Bound ◽  
S. D. Standfield ◽  
B. Gedulin ◽  
K. L. Jones ◽  
...  
Keyword(s):  
Peptide Yy ◽  
Rectal Administration ◽  
Taurocholic Acid ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans

1997 ◽  
Vol 273 (5) ◽  
pp. E981-E988 ◽  
Author(s):  
Michael A. Nauck ◽  
Ulrich Niedereichholz ◽  
Rainer Ettler ◽  
Jens Juul Holst ◽  
Cathrine Ørskov ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Normal Subjects ◽  
Diabetic Patients ◽  
Phenol Red ◽  
Type 2 Diabetic Patients ◽  
Liquid Meal ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Insulin Responses

Glucagon-like peptide 1 (GLP-1) has been shown to inhibit gastric emptying of liquid meals in type 2 diabetic patients. It was the aim of the present study to compare the action of physiological and pharmacological doses of intravenous GLP-1-(7—36) amide and GLP-1-(7—37) on gastric emptying in normal volunteers. Nine healthy subjects participated (26 ± 3 yr; body mass index 22.9 ± 1.6 kg/m2; hemoglobin A1C 5.0 ± 0.2%) in five experiments on separate occasions after an overnight fast. A nasogastric tube was positioned for the determination of gastric volume by use of a dye-dilution technique (phenol red). GLP-1-(7—36) amide (0.4, 0.8, or 1.2 pmol ⋅ kg−1 ⋅ min−1), GLP-1-(7—37) (1.2 pmol ⋅ kg−1 ⋅ min−1), or placebo was infused intravenously from −30 to 240 min. A liquid meal (50 g sucrose, 8% amino acids, 440 ml, 327 kcal) was administered at 0 min. Glucose, insulin, and C-peptide were measured over 240 min. Gastric emptying was dose dependently slowed by GLP-1-(7—36) amide ( P < 0.0001). Effects of GLP-1-(7—37) at 1.2 pmol ⋅ kg−1 ⋅ min−1were virtually identical. GLP-1 dose dependently stimulated fasting insulin secretion (−30 to 0 min) and slightly reduced glucose concentrations. After the meal (0–240 min), integrated incremental glucose ( P < 0.0001) and insulin responses ( P = 0.01) were reduced (dose dependently) rather than enhanced. In conclusion, 1) GLP-1-(7—36) amide or -(7—37) inhibits gastric emptying also in normal subjects, 2) physiological doses (0.4 pmol ⋅ kg−1 ⋅ min−1) still have a significant effect, 3) despite the known insulinotropic actions of GLP-1-(7—36) amide and -(7—37), the net effect of administering GLP-1 with a meal is no change or a reduction in meal-related insulin responses. These findings suggest a primarily inhibitory function for GLP-1 (ileal brake mechanisms).

scholarly journals Exenatide, a Glucagon-like Peptide-1 Receptor Agonist, Acutely Inhibits Intestinal Lipoprotein Production in Healthy Humans

2012 ◽  
Vol 32 (6) ◽  
pp. 1513-1519 ◽  
Author(s):  
Changting Xiao ◽  
Robert H. J. Bandsma ◽  
Satya Dash ◽  
Linda Szeto ◽  
Gary F. Lewis
Keyword(s):  
Receptor Agonist ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

scholarly journals Ghrelin Impairs Prandial Glucose Tolerance and Insulin Secretion in Healthy Humans Despite Increasing GLP-1

2016 ◽  
Vol 101 (6) ◽  
pp. 2405-2414 ◽  
Author(s):  
Jenny Tong ◽  
Harold W. Davis ◽  
Amalia Gastaldelli ◽  
David D'Alessio
Keyword(s):  
Insulin Secretion ◽  
Steady State ◽  
Glucose Tolerance ◽  
Healthy Subjects ◽  
Tolerance Test ◽  
Β Cell ◽  
Meal Tolerance Test ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Objectives: Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fasting and feeding. Our objective was to test the effects of ghrelin on glucose and insulin responses during a meal tolerance test. Design: Acyl ghrelin (0.26 and 2.0 μg/kg/h) or saline was infused in 13 healthy subjects on three separate occasions in randomized order. Ghrelin was infused for 45 minutes to achieve steady-state levels and continued for 240 minutes after ingestion of a liquid test meal. Primary outcomes were area under the curve for glucose and insulin secretion. Results: We found that ghrelin infusions of 0.26 and 2.0 μg/kg/h raised steady-state plasma total ghrelin levels to 1.7- and 4.8-fold above fasting concentrations, but did not alter fasting plasma glucose or insulin levels. During the meal tolerance test, ghrelin decreased insulin sensitivity, impaired β-cell function, and induced glucose intolerance. The high-dose ghrelin infusion also raised postprandial glucagon like peptide 1 secretion without affecting glucose dependent insulinotropic polypeptide, glucagon, or peptide YY concentrations. Conclusions: We conclude that both physiologic and pharmacologic doses of ghrelin worsen the glucose and β-cell responses to meal ingestion in healthy humans. The increase in postprandial glucagon like peptide 1 secretion by ghrelin suggests a novel enteroendocrine connection, but does not mitigate the glucose intolerance.

Abstract 95: Glucagon Like Peptide-1 (GLP-1) Does Not Cause Vasodilation Even When Dipeptidyl Peptidase 4 (DPP4) is Inhibited

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Jessica K Devin ◽  
Mias Pretorius ◽  
Frederic T Billings ◽  
Hui Nian ◽  
Nancy J Brown
Keyword(s):  
Interactive Effect ◽  
Dipeptidyl Peptidase ◽  
Diabetic Patients ◽  
Baseline Heart Rate ◽  
Dipeptidyl Peptidase 4 ◽  
Dpp4 Inhibitors ◽  
Healthy Humans ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Dpp4 Inhibition

Glucagon-like peptide 1 (GLP-1) causes direct vasodilation in animal models. Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control in diabetic patients by preventing the degradation of GLP-1. The direct effect of GLP-1 in the human vasculature, and how it is altered by DPP4 inhibition, has not been reported. This study tested the hypothesis that intra-arterial infusion of GLP-1 causes dose-dependent vasodilation, and that DPP4 inhibition potentiates the forearm blood flow (FBF) response to GLP-1 by decreasing its degradation. Eight healthy, non-obese (BMI<30 kg/m 2 ) subjects, age 28-54 years old (3 female) participated in this double-blind, placebo-controlled crossover study. On study days separated by at least one week subjects received DPP4 inhibitor (sitagliptin 200 mg p.o.) or placebo, followed by infusion of GLP-1 in the brachial artery at graded doses (0.45-3.60 pmol/min) for 5 minutes per dose. Sitagliptin significantly decreased plasma DPP4 activity (p<0.001 vs. placebo). Sitagliptin did not significantly affect baseline heart rate or baseline FBF. Baseline mean arterial pressure was significantly higher during sitagliptin than during placebo [87.13 ± 2.10 mmHg versus 84.75 ± 3.28 mmHg, p=0.037]. GLP-1 concentrations were significantly higher after sitagliptin (Left Figure; N=5). There was no effect of GLP-1 on FBF either in the presence or absence of sitagliptin. Moreover, there was no interactive effect of GLP-1 and sitagliptin on FBF (Right Figure). GLP-1 does not cause vasodilation in healthy humans even when its degradation is inhibited. These data have implications for the cardiovascular effects of DPP4 inhibitors and GLP-1 receptor agonists.

scholarly journals Influences of Hypoxia Exercise on Whole-Body Insulin Sensitivity and Oxidative Metabolism in Older Individuals

2019 ◽  
Vol 104 (11) ◽  
pp. 5238-5248 ◽  
Author(s):  
Kristine Chobanyan-Jürgens ◽  
Renate J Scheibe ◽  
Arne B Potthast ◽  
Markus Hein ◽  
Andrea Smith ◽  
...  
Keyword(s):  
Heart Rate ◽  
Insulin Sensitivity ◽  
Oxidative Metabolism ◽  
Perceived Exertion ◽  
Glucose Clamp ◽  
Normobaric Hypoxia ◽  
Metabolic Effects ◽  
Whole Body ◽  
Fraction Of Inspired Oxygen ◽  
Inspired Oxygen

Abstract Context Aging is a primary risk factor for most chronic diseases, including type 2 diabetes. Both exercise and hypoxia regulate pathways that ameliorate age-associated metabolic muscle dysfunction. Objective We hypothesized that the combination of hypoxia and exercise would be more effective in improving glucose metabolism than normoxia exercise. Design and Participants We randomized 29 older sedentary individuals (62 ± 6 years; 14 women, 15 men) to bicycle exercise under normobaric hypoxia (fraction of inspired oxygen = 15%) or normoxia (fraction of inspired oxygen = 21%). Intervention Participants trained thrice weekly for 30 to 40 minutes over 8 weeks at a heart rate corresponding to 60% to 70% of peak oxygen update. Main Outcome Measures Insulin sensitivity measured by hyperinsulinemic-euglycemic glucose clamp and muscle protein expression before and after hyperinsulinemic-euglycemic glucose clamp. Results Heart rate and perceived exertion during training were similar between groups, with lower oxygen saturation when exercising under hypoxia (88.7 ± 1.5 vs 96.2 ± 1.2%, P < 0.01). Glucose infusion rate after 8 weeks increased in both the hypoxia (5.7 ± 1.1 to 6.7 ± 1.3 mg/min/kg; P < 0.01) and the normoxia group (6.2 ± 2.1 to 6.8 ± 2.1 mg/min/kg; P = 0.04), with a mean difference between groups of –0.44 mg/min/kg; 95% CI, –1.22 to 0.34; (P = 0.25). Markers of mitochondrial content and oxidative capacity in skeletal muscle were similar after training in both groups. Changes in Akt phosphorylation and glucose transporter 4 under fasting and insulin-stimulated conditions were not different between groups over time. Conclusions Eight weeks of hypoxia endurance training led to similar changes in insulin sensitivity and markers of oxidative metabolism compared with normoxia training. Normobaric hypoxia exercise did not enhance metabolic effects in sedentary older women and men beyond exercise alone.

scholarly journals Glucagon, GLP-1 and Thermogenesis

2019 ◽  
Vol 20 (14) ◽  
pp. 3445 ◽  
Author(s):  
Ismael González-García ◽  
Edward Milbank ◽  
Carlos Diéguez ◽  
Miguel López ◽  
Cristina Contreras
Keyword(s):  
Energy Expenditure ◽  
Direct Action ◽  
Short Review ◽  
Obesity And Diabetes ◽  
Promising Target ◽  
Brown Adipose ◽  
Endocrine Factors ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Maintain Body Temperature

Brown adipose tissue (BAT) thermogenesis is a conserved mechanism to maintain body temperature in mammals. However, since BAT contribution to energy expenditure can represent a relevant modulator of metabolic homeostasis, many studies have focused on the nervous system and endocrine factors that control the activity of this tissue. There is long-established evidence that the counter-regulatory hormone glucagon negatively influences energy balance, enhances satiety, and increases energy expenditure. Despite compelling evidence showing that glucagon has direct action on BAT thermogenesis, recent findings are questioning this conventional attribute of glucagon action. Glucagon like peptide-1 (GLP-1) is an incretin secreted by the intestinal tract which strongly decreases feeding, and, furthermore, improves metabolic parameters associated with obesity and diabetes. Therefore, GLP-1 receptors (GLP-1-R) have emerged as a promising target in the treatment of metabolic disorders. In this short review, we will summarize the latest evidence in this regard, as well as the current therapeutic glucagon- and GLP-1-based approaches to treating obesity.

scholarly journals Glucagon-like peptide 1 and fatty acids amplify pulsatile insulin secretion from perifused rat islets

2003 ◽  
Vol 369 (1) ◽  
pp. 173-178 ◽  
Author(s):  
Barbara A. CUNNINGHAM ◽  
Ann-Marie T. RICHARD ◽  
Joseph S. DILLON ◽  
Jennifer T. DALEY ◽  
Vildan N. CIVELEK ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Phosphodiesterase Inhibitor ◽  
Time Interval ◽  
Rat Islets ◽  
Healthy Humans ◽  
Therapeutic Uses ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Perifused Islets ◽  
Pulsatile Insulin Secretion

Glucose-induced insulin secretion from isolated, perifused rat islets is pulsatile with a period of about 5—10min, similar to the insulin oscillations that are seen in healthy humans but which are impaired in Type II diabetes. We evaluated the pattern of enhancement by the potent incretin, glucagon-like peptide 1 (GLP-1). GLP-1 increased the amplitude of pulses and the magnitude of insulin secretion from the perifused islets, without affecting the average time interval between pulses. Forskolin and the phosphodiesterase inhibitor isobutylmethylxanthine had the same effect, suggesting that the effect was due to elevated cAMP levels. The possibility that cAMP might enhance the amplitude of pulses by reducing phosphofructo-2-kinase (PFK-2) activity was eliminated when the liver isoform of PFK-2 was shown to be absent from β-cells. The possibility that cAMP enhanced pulsatile secretion, at least in part, by stimulating lipolysis was supported by the observations that added oleate had a similar effect on secretion, and that the incretin effect of GLP-1 was inhibited by the lipase inhibitor orlistat. These data show that the physiological incretin GLP-1 preserves and enhances normal pulsatile insulin secretion, which may be essential in proposed therapeutic uses of GLP-1 or its analogues.

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