Authors: Lovshin, J; Drucker, DJ

Source: Pediatric Diabetes, Volume 1, Number 1, March 2000 , pp. 49-57(9)

Publisher: Wiley-Blackwell

Abstract:

Glucagon-like peptides-1 and -2 (GLP-1 and GLP-2) are co-encoded along with glucagon in a single mammalian proglucagon gene that is expressed in islets and enteroendocrine L cells of the small and large intestine. Both peptides are liberated following cleavage by prohormone convertase 1/3 and secreted from the intestine following nutrient ingestion. A key determinant of GLP-1 and GLP-2 bioactivity is the enzyme dipeptidyl peptidase-IV, which inactivates both peptides by cleavage at the position-2 alanine. GLP-1 regulates blood glucose via actions on gastric emptying and islet hormones, including the regulation of insulin, glucagon, and somatostatin secretion. GLP-1 action is essential for β-cell function, because the disruption of GLP-1 signaling results in reduced insulin secretion, decreased islet cyclic adenosine monophosphate, and abnormal intracellular calcium oscillations. GLP-1 also decreases appetite and induces satiety in human subjects, and inhibits food intake in rodents following intracerebroventricular administration. GLP-2 does not appear to directly regulate blood glucose, but contributes to nutrient assimilation via trophic effects on the intestinal mucosa. GLP-2 also decreases apoptosis in the crypts and villi, reduces intestinal epithelial permeability, and promotes intestinal glucose transport. The actions of GLP-1 and GLP-2 in experimental models of diabetes or intestinal injury, respectively, suggest that GLP-1 may be useful for the treatment of human diabetes, whereas GLP-2 may be of therapeutic benefit in patients with intestinal injury and compromised nutrient assimilation.

Keywords: bowel; diabetes; glucagon-like peptide-1 (GLP-1); glucagon-like peptide-2 (GLP-2); gut; intestinal disease

Document Type: Review article

DOI: http://dx.doi.org/10.1034/j.1399-5448.2000.010108.x

Publication date: 2000-03-01

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