Minireview: the glucagon-like peptides.
The glucagon-like peptides GLP-1 and GLP-2 are produced in enteroendocrine L cells of the small and large intestine and secreted in a nutrient-dependent manner. GLP-1 regulates nutrient assimilation via inhibition of gastric emptying and food intake. GLP-1 controls blood glucose following nutrient absorption via stimulation of glucose-dependent insulin secretion, insulin biosynthesis, islet proliferation, and neogenesis and inhibition of glucagon secretion. Experiments using GLP-1 antagonists and GLP-1 receptor-/- mice indicate that the glucoregulatory actions of GLP-1 are essential for glucose homeostasis. In the central nervous system, GLP-1 regulates hypothalamic-pituitary function and GLP-1-activated circuits mediate the CNS response to aversive stimulation. GLP-2 maintains the integrity of the intestinal mucosal epithelium via effects on gastric motility and nutrient absorption, crypt cell proliferation and apoptosis, and intestinal permeability. Both GLP-1 and GLP-2 are rapidly inactivated in the circulation as a consequence of amino-terminal cleavage by the enzyme dipeptidyl peptidase IV (DP IV). The actions of these peptides on nutrient absorption and energy homeostasis and the efficacy of GLP-1 and GLP-2 in animal models of diabetes and intestinal diseases, respectively, suggest that analogs of these peptides may be clinically useful for the treatment of human disease.
Drucker
D J
DJ
Department of Medicine, Toronto General Hospital, Banting and Best Diabetes Centre, University of Toronto, Toronto, Ontario M5G 2C4 Canada. d.drucker@utoronto.ca
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy; D005934:Glucagon / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D052216:Glucagon-Like Peptide 1; D053767:Glucagon-Like Peptide 2; D006801:Humans; D007410:Intestinal Diseases / Q000188:drug therapy; D007422:Intestines / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use; D011498:Protein Precursors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology* / Q000627:therapeutic use
D053767:Glucagon-Like Peptide 2; D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon