Glucagon-like peptide-1(GLP-1)<\/a> and glucose-depended insulinotropic polypeptide<\/a> GLP-1, another incretin hormone, was identified after the cloning and sequencing\u00a0of the cDNA and genes encoding human proglucagon. The proglucagon gene\u00a0encodes two peptides that share about 50% sequence homology to glucagon. The two\u00a0peptides were named glucagon-like peptide-1 (GLP-1) and glucogan-like peptide-2\u00a0(GLP-2). After tissue-specific proteolytically posttranslational processing, GLP-1 is\u00a0released from L cell of lower intestine and colon in response to nutrient ingestion.\u00a0GLP-1 stimulates glucose-dependent insulin secretion in isolated islets as well as in\u00a0human, whereas GLP-2 was unable to stimulate insulin secretion and is not\u00a0an incretin hormone.<\/p>\n Regulation of GLP-1\u00a0and GIP secretion<\/p>\n
\n(GIP)<\/a> are the two peptides that have been confirmed to act as incretin hormones to
\ndate. GIP was the first incretin hormone identified. It was originally isolated from
\ncrude extracts of porcine small intestine. Based on its ability to inhibit gastric acid
\nsecretion in dogs, it was initially named gastric inhibitory polypeptide <\/em>(GIP),.\u00a0Using more purified GIP, Dupre et al. <\/em>showed that GIP could also stimulate\u00a0insulin secretion in animals and human. Subsequently, it was found that GIP can act\u00a0directly on pancreatic islets to stimulate insulin secretion. Since the effect of\u00a0GIP on stimulation of insulin secretion was seen at physiologic levels while inhibitory\u00a0effect of GIP on gastric acid secretion occurred at pharmacologic doses, GIP was then\u00a0renamed glucose-dependent insulinotropic polypeptide in order to reflect its\u00a0physiologic action. Secreted from K cell of the proximal small intestine, GIP is\u00a0stimulated by enteral glucose, lipids, and products of meal digestion in a\u00a0dose-dependent manner. Further studies showed that GIP only contributes to the\u00a0partial incretin effect in vivo<\/em>, because immunological depletion of GIP reduced but\u00a0did not abolish all insulin-stimulating activity of gut extracts.<\/p>\n