[Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2].

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Diamant M, Bunck MC, Heine RJ

[Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2].

Ned Tijdschr Geneeskd. 2004 Sep 25;148(39):1912-7.

PubMed ID

15495988 [ View in PubMed

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Abstract

Upon ingestion of food, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are synthesised and secreted by specialised gut cells. GLP-1 is also produced in the pancreatic islets and the central nervous system. Both incretins bind to specific G-protein-coupled receptors that are distributed throughout the body. Incretins potentiate meal-induced insulin production and secretion by the beta-cells and lower the blood glucose level in the presence of hyperglycaemia. GLP-1 and GIP stimulate beta-cell proliferation and differentiation, whereas GLP-1 only inhibits gastric emptying and glucagon secretion, reduces food intake and improves insulin sensitivity. Insulin-resistant and type-2 diabetic patients have an impaired incretin response to meal ingestion. However, the insulinotropic action of exogenous GLP-1, but not that of GIP, is preserved in these subjects. After parenteral administration, GLP-1 has an extremely short duration of action because it is rapidly degraded by the ubiquitous enzyme dipeptidyl peptidase IV (DPPIV). To prolong GLP-1 bioactivity, DPPIV-resistant GLP-1 analogues, DPPIV inhibitors and exenatide, a long-acting synthetic GLP-1 receptor agonist derived from the Gila monster hormone exendin-4, have been developed. Enhancement of incretin action seems a rational and promising option for the treatment of type-2 diabetes.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Exenatide	Glucagon-like peptide 1 receptor	Protein	Humans	Yes	Agonist	Details