Clinical Gastroenterology Vol.31 No.9(1-3)

Theme The Gastrointestinal Tract and Appetite Control : Essential Clinical Knowledge
Title Diabetes and Gastrointestinal Tract
Publish Date 2016/08
Author Shunsuke Yamane Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
Author Nobuya Inagaki Department of Diabetes, Endocrinology and Nutrition, Graduate School of Medicine, Kyoto University
[ Summary ] Enteroendocrine hormones released in response to oral nutrient intake include incretins, gastric inhibitory polypeptide (GIP), and glucagon‒like peptide‒1 (GLP‒1), which are responsible for 50 to 60 % of the postprandial insulin secretion. GIP is secreted from K‒cells in the proximal small intestine, whereas GLP‒1 is secreted from L‒cells in the distal small intestine and colon. They both binds to their respective receptors on the surface of pancreatic β‒cells to stimulate insulin secretion. Rapid degradation of incretins by dipeptidyl peptidase‒4 (DPP‒4) and rapid renal clearance of incretin molecules result in a half‒life of 1 to 2 minutes. Besides its insulinotropic action, GLP‒1 has various physiological functions that are beneficial for the treatment of type 2 diabetes (T2DM). Two classes of incretin‒based therapies were developed to target hyperglycemia in T2DM : GLP‒1 receptor agonists and inhibitors of the GLP‒1 degrading enzyme (DPP‒4 inhibitors). In this review, we will describe the underlying mechanisms of GLP‒1 function and discuss the potential beneficial and adverse effects of incretin‒based therapies.
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