Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)

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R-HSA-381771
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Homo sapiens
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In L cells of the intestine the transcription factors TCF-4 (TCF7L2) and Beta-catenin form a heterodimer and bind the G2 enhancer of the Proglucagon gene GCG,activating its transcription to yield Proglucagon mRNA and, following translation, Proglucagon protein. The prohormone convertase PC1 present in the secretory granules of L cells cleaves Proglucagon at two sites to yield mostly Glucagon-like Peptide-1 (7-36) with a small amount of Glucagon-like Peptide-1 (7-37). Glucagon-like Peptide-1 (7-36 and 7-37) (GLP-1) is secreted into the bloodstream in response to glucose, fatty acids, insulin, leptin, gastrin-releasing peptide, cholinergic transmitters, beta-adrenergic transmitters, and peptidergic transmitters. The half-life of GLP-1 in the bloodstream is determined by Dipeptidyl Peptidase IV, which cleaves 2 amino acids at the amino terminus of GLP-1, rendering it biologically inactive.

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
17928588 The physiology of glucagon-like peptide 1

Holst, JJ

Physiol Rev 2007
17263764 Incretins and other peptides in the treatment of diabetes

Todd, JF, Bloom, SR

Diabet Med 2007
11564718 A human cellular model for studying the regulation of glucagon-like peptide-1 secretion

Reimer, RA, Darimont, C, Gremlich, S, Nicolas-Métral, V, Rüegg, UT, Macé, K

Endocrinology 2001
17498508 Biology of incretins: GLP-1 and GIP

Baggio, LL, Drucker, DJ

Gastroenterology 2007
1499644 Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man

Eissele, R, Göke, R, Willemer, S, Harthus, HP, Vermeer, H, Arnold, R, Göke, B

Eur J Clin Invest 1992
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