Is glucagon-like peptide 1 an incretin hormone?
Glucagon-like peptide-1 (GLP-1) was predicted, based on the proglucagon gene sequence. It is synthesised by specific post-translational processing in L cells (lower intestine) and secreted mainly as "truncated" GLP-1 [7-36 amide] in response to nutrient ingestion. Glucagon-like peptide-1 stimulates insulin secretion during hyperglycaemia, suppresses glucagon secretion, stimulates (pro)insulin biosynthesis and decelerates gastric emptying and acid secretion. On intracerebroventricular injection, GLP-1 reduces food intake in rodents. A GLP-1 receptor antagonist or GLP-1 antisera have been shown to reduce meal-stimulated insulin secretion in animals, suggesting that GLP-1 has a physiological "incretin" function (augmentation of postprandial insulin secretion due to intestinal hormones) for GLP-1. In healthy human subjects, exogenous GLP-1 slows gastric emptying. Consequently, postprandial insulin secretion is reduced, not augmented. Thus, a participation of this peptide in the incretin effect of non-diabetic humans has not been definitely proven. Nevertheless, it has potent insulinotropic activity, especially during hyperglycaemia. This suggests new therapeutic options for patients with Type II (non-insulin-dependent) diabetes mellitus. On the other hand, most L cells are located in the lower small intestine. Potent inhibitory actions of GLP-1 on upper gastrointestinal motor and digestive functions (e. g. gastric emptying and acid secretion) in response to nutrients placed into the ileal lumen, argue for a role of this peptide as an "ileal brake". Malassimilation and diarrhea leading to the erroneous presence of nutrients in the lower gut may, via GLP-1, delay gastric emptying and reduce upper gut motility and thereby prevent further caloric losses.
Nauck
M A
MA
Department of Medicine, Knappschafts-Krankenhaus, Ruhr-University Bochum, Germany.
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000628:therapy; D004063:Digestion / Q000187:drug effects; D005746:Gastric Emptying / Q000187:drug effects; D005768:Gastrointestinal Hormones / Q000502:physiology*; D005769:Gastrointestinal Motility / Q000187:drug effects; D005934:Glucagon / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D011498:Protein Precursors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*
D005768:Gastrointestinal Hormones; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon