Is Glucagon-Like Peptide 1 an Incretin Hormone?

Diabetologia. 1999 Mar;42(3):373-9. doi: 10.1007/s001250051165.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / therapy
  • Digestion / drug effects
  • Gastric Emptying / drug effects
  • Gastrointestinal Hormones / physiology*
  • Gastrointestinal Motility / drug effects
  • Glucagon / genetics
  • Glucagon / pharmacology
  • Glucagon / physiology*
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptides
  • Humans
  • Insulin / metabolism
  • Insulin Secretion
  • Peptide Fragments / genetics
  • Peptide Fragments / pharmacology
  • Peptide Fragments / physiology*
  • Protein Precursors / genetics
  • Protein Precursors / pharmacology
  • Protein Precursors / physiology*

Substances

  • Gastrointestinal Hormones
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon