Incretin synthesis, secretion, and inactivation

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Homo sapiens
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Incretins are peptide hormones produced by the gut that enhance the ability of glucose to stimulate insulin secretion from beta cells in the pancreas. Two incretins have been identified: Glucagon-like Peptide-1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP, initially named Gastric Inhibitory Peptide). Both are released by cells of the small intestine, GLP-1 from L cells and GIP from K cells.
The control of incretin secretion is complex. Fatty acids, phospholipids, glucose, acetylcholine, leptin, and Gastrin-releasing Peptide all stimulate secretion of GLP-1. Fatty acids and phospholipids are the primary stimulants of secretion of GIP in humans (carbohydrates have more effect in rodents).
Incretins secreted into the bloodstream are subject to rapid inactivation by Dipeptidyl Peptidase IV (DPP IV), which confers half-lives of only a few minutes onto GLP-1 and GIP. Inhibitors of DPP IV, for example sitagliptin, are now being used in the treatment of Type 2 diabetes.

Literature References
PubMed ID Title Journal Year
19074620 The role of incretins in glucose homeostasis and diabetes treatment

Kim, W, Egan, JM

Pharmacol Rev 2008
17263764 Incretins and other peptides in the treatment of diabetes

Todd, JF, Bloom, SR

Diabet Med 2007
17498508 Biology of incretins: GLP-1 and GIP

Drucker, DJ, Baggio, LL

Gastroenterology 2007
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