glucagon-like-peptide-1 and Starvation

The impact of bariatric surgery on insulin sensitivity and glucose tolerance has refocused interest in the role of gut-derived factors in the regulation of insulin secretion and action. The incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) are released from endocrine cells in the small intestinal mucosa primarily in response to oral nutrient ingestion. They have various effects, including augmentation of glucose-stimulated insulin secretion (GSIS), actions that promote the cellular assimilation and storage of dietary glucose and lipid as liver and skeletal muscle glycogen and adipocyte triacylglycerol (TAG) respectively. Similarly, increased delivery of fatty acids (FA) acutely augments GSIS, and the resultant enhancement of GSIS facilitates FA storage as adipocyte TAG. Leptin secretion from white adipocytes curbs appetite to limit dietary nutrient intake and adipocyte TAG storage and, potentially, GSIS, thereby curtailing insulin-dependent TAG storage. On fasting, GSIS is curbed, an effect the mechanism of which is even now incompletely understood, but which may reflect augmented β-cell FA oxidation. The orexigen ghrelin, systemic concentrations of which increase with fasting, exerts enigmatic effects on GSIS, in that acylated ghrelin and unacylated ghrelin exert opposing effects on GSIS, whereas acylated ghrelin and unacylated ghrelin share protective effects on islet survival. This review will build on these emerging studies to evaluate the roles of the incretins, leptin, lipids and acylated and unacylated ghrelin in modulating islet function and survival during feasting and fasting.

Topics: Fasting; Ghrelin; Glucagon-Like Peptide 1; Humans; Incretins; Insulin; Insulin Secretion; Insulin-Secreting Cells; Leptin; Satiation; Signal Transduction; Starvation

Topics: Animals; Eating; Energy Metabolism; Exercise; Exercise Test; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Homeostasis; Hormones; Humans; Oxygen Consumption; Peptide Fragments; Peptides; Protein Precursors; Secretin; Starvation; Vasoactive Intestinal Peptide

Postprandial glucose is reduced in malnourished patients with anorexia nervosa (AN), but the mechanisms and duration for this remain unclear. We examined blood glucose, gastric emptying, and glucoregulatory hormone changes in malnourished patients with AN and during 2 wk of acute refeeding compared with healthy controls (HCs). Twenty-two female adolescents with AN and 17 age-matched female HCs were assessed after a 4-h fast. Patients were commenced on a refeeding protocol of 2,400 kcal/day. Gastric emptying (

Topics: 3-O-Methylglucose; Adolescent; Anorexia Nervosa; Blood Glucose; Breath Tests; C-Peptide; Caprylates; Carbon Isotopes; Case-Control Studies; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Postprandial Period; Starvation; Young Adult

To determine whether starvation affects the metabolism of glucagon-like peptide-1 (GLP-1), we measured the plasma levels of proglucagon-derived peptides and the biosynthesis and posttranslational processing of proglucagon in groups of six rats starved for 1, 3 and 5 days. The plasma levels of GLP-1 immunoreactivity (GLP-1 IR) and glucagon-like immunoreactivity (GLI) decreased during starvation reaching 79 and 56% of the respective control values by day 5 (P less than 0.05 and less than 0.01 vs control). The same is true of the plasma IRI level. The ileal contents of GLP-1 IR and GLI were 50.8 +/- 3.8 pmol/g wet weight and 161.8 +/- 13.2 pmol/g wet weight, respectively, on day 5 of starvation, which were significantly lower (P less than 0.01) than the respective values of 94.8 +/- 16.6 pmol/g wet weight and 262.7 +/- 28.1 pmol/g wet weight in control rats. However, the pancreatic contents of proglucagon-derived peptides tended to increase during starvation, although their increases were not statistically significant. No significant change in the posttranslational processing of proglucagon was detected during starvation. The decrease in the ileal proglucagon-derived peptides content was not associated with a decrease in intestinal proglucagon mRNA transcripts. These results suggested that decreased synthesis of proglucagon-derived peptides by the intestine was largely responsible for the reductions in their circulating levels in starved rats.

Topics: Analysis of Variance; Animals; Body Weight; Chromatography, High Pressure Liquid; Fasting; Glucagon; Glucagon-Like Peptide 1; Ileum; Insulin; Male; Peptide Fragments; Proglucagon; Protein Precursors; Protein Processing, Post-Translational; Rats; Rats, Inbred Strains; Reference Values; RNA; Starvation; Time Factors

The effects of i.v. glucagon-like peptide-1-(7-36)amide (GLP-1; 10 micrograms) on starved sheep given an i.v. glucose load (5 g) were studied. Plasma insulin concentrations rose significantly more after glucose administration in fed than in starved sheep. Giving GLP-1 to starved sheep increased the insulin response to the glucose load. The rise in plasma insulin concentrations in starved sheep given GLP-1 was similar to that observed in fed sheep. Plasma glucose concentrations returned to normal values more quickly in the starved sheep given GLP-1 than in starved sheep not given gut hormone. Plasma concentrations of free fatty acid, urea and alpha-amino nitrogen decreased more quickly following glucose administration in starved sheep given GLP-1 than in those not given GLP-1. The data suggest a role for GLP-1 in regulating plasma insulin concentrations and hence metabolism in ruminant animals. The possible role of gut hormones in ruminants is discussed.

Topics: Animals; Fatty Acids, Nonesterified; Glucagon; Glucagon-Like Peptide 1; Glucose; Insulin; Peptide Fragments; Protein Precursors; Sheep; Starvation; Urea