The multiple actions of GLP-1 on the process of glucose-stimulated insulin secretion.
The physiological effects of glucagon-like peptide-1 (GLP-1) are of immense interest because of the potential clinical relevance of this peptide. Produced in intestinal L-cells through posttranslational processing of the proglucagon gene, GLP-1 is released from the gut in response to nutrient ingestion. Peripherally, GLP-1 is known to affect gut motility, inhibit gastric acid secretion, and inhibit glucagon secretion. In the central nervous system, GLP-1 induces satiety, leading to reduced weight gain. In the pancreas, GLP-1 is now known to induce expansion of insulin-secreting beta-cell mass, in addition to its most well-characterized effect: the augmentation of glucose-stimulated insulin secretion. GLP-1 is believed to enhance insulin secretion through mechanisms involving the regulation of ion channels (including ATP-sensitive K(+) channels, voltage-dependent Ca(2+) channels, voltage-dependent K(+) channels, and nonselective cation channels) and by the regulation of intracellular energy homeostasis and exocytosis. The present article will focus principally on the mechanisms proposed to underlie the glucose dependence of GLP-1's insulinotropic effect.
MacDonald
Patrick E
PE
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
El-Kholy
Wasim
W
Riedel
Michael J
MJ
Salapatek
Anne Marie F
AM
Light
Peter E
PE
Wheeler
Michael B
MB
D000818:Animals; D005934:Glucagon / Q000502:physiology*; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D010179:Pancreas / Q000378:metabolism; D010446:Peptide Fragments / Q000502:physiology*; D011498:Protein Precursors / Q000502:physiology*
D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose