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-depende nt manner. GLP-1 regulates nutrient assimilation via inhibition of gastric emptying and food intake. GLP-1 controls blood glucose following nutrient a bsorption via stimulation of glucose-dependent insulin secretion, insulin b iosynthesis, 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 glucos e 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 muco sal epithelium via effects on gastric motility and nutrient absorption, cry pt 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 intestina l diseases, respectively, suggest that analogs of these peptides may be cli nically useful for the treatment of human disease.