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This website, sponsored by Merck Sharpe and Dohme, addresses an important mechanism of glucose homeostasis—the coordinated function of pancreatic beta cells and alpha cells—and sheds light on the incretins, important mediators of that mechanism.
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| GIP and GLP-1 |
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GIP and GLP-1 are the two major incretin hormones in humans.1,2
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- K Cells—Proximal GI Tract
GIP is a 42–amino-acid peptide derived from a larger protein (ProGIP) and is secreted by endocrine K cells mainly present in the proximal gastrointestinal (GI) tract (duodenum and proximal jejunum).2,3
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- L Cells—Distal GI Tract
GLP-1 is a 30–amino-acid or 31–amino-acid peptide derived from a larger protein (proglucagon) and is secreted by L cells located predominantly in the distal GI tract (ileum and colon).2,3
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The glucose-regulating actions of GLP-1 and GIP are mediated through the binding and activation of their respective receptors (GLP-1R and GIP-R) located in several tissues, including alpha and beta cells in the pancreatic islets.2
In the fasting state, plasma levels of GLP-1 and GIP are low2; however, the secretion of GLP-1 and GIP rapidly increases after eating a meal.2,5
- After secretion, GLP-1 and GIP are rapidly metabolized by the enzyme DPP-4.4 The plasma half-life of these incretins is short (approximately 2 minutes for intact GLP-1 and up to 5 minutes for GIP).6
- Following rapid degradation, the metabolites of GLP-1 and GIP are eliminated through the kidney.6-8
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