Processing of Proglucagon to Glucagon-like Peptide-1 Secretion of Glucagon-like Peptide 1 from Intestinal L Cells Processing of preproGLP-1 to proGLP-1 Transit of Proglucagon from the ER Lumen to Secretory Granules Proteolytic Cleavage of Glucagon-like Peptide-1 (GLP-1) PathwayStep2052 PathwayStep2053 PathwayStep2054 PathwayStep2055 PathwayStep2056 PathwayStep2057 Synthesis of Preproglucagon in Intestinal L Cells Synthesis, Secretion, and Inactivation of Glucagon-like Peptide-1 (GLP-1) Authored: May, B, 2009-05-18 21:31:59 Edited: May, B, 2009-09-09 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. Pubmed11564718 Pubmed1499644 Pubmed17263764 Pubmed17498508 Pubmed17928588 Pubmed19074620 Reactome Database ID Release 43381771 Reactome, http://www.reactome.org ReactomeREACT_24019 Reviewed: Bloom, SR, 2010-06-24