Minireview: The Glucagon-Like Peptides

• Published in: Endocrinology (Philadelphia) Vol. 142; no. 2; pp. 521 - 527
• Main Author: Drucker, Daniel J
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.02.2001
• Subjects: Animals; Central Nervous System - drug effects; Diabetes Mellitus - drug therapy; Glucagon - metabolism; Glucagon - pharmacology; Glucagon - physiology; Glucagon - therapeutic use; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestinal Diseases - drug therapy; Intestines - drug effects; Pancreas - drug effects; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Peptide Fragments - physiology; Peptide Fragments - therapeutic use; Peptides - metabolism; Peptides - pharmacology; Peptides - physiology; Peptides - therapeutic use; Protein Precursors - metabolism; Protein Precursors - pharmacology; Protein Precursors - physiology; Protein Precursors - therapeutic use
• ISSN: 0013-7227; 1945-7170
• DOI: 10.1210/endo.142.2.7983

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.