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Synthesis, secretion and biological actions of the glucagon‐like peptides
Author(s) -
Lovshin J,
Drucker DJ
Publication year - 2000
Publication title -
pediatric diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.678
H-Index - 75
eISSN - 1399-5448
pISSN - 1399-543X
DOI - 10.1034/j.1399-5448.2000.010108.x
Subject(s) - proglucagon , medicine , endocrinology , glucagon like peptide 2 , glucokinase , islet , enteroendocrine cell , glucagon like peptide 1 , glucagon , gastric emptying , prohormone convertase , insulin , biology , prohormone , hormone , diabetes mellitus , type 2 diabetes , biochemistry , stomach , endocrine system , peptide
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.