A novel pathway for regulation of glucose-dependent insulinotropic polypeptide (GIP) receptor expression in beta cells.

作者: Francis C. Lynn , Stephen A. Thompson , J. Andrew Pospisilik , Jan A. Ehses , Simon A. Hinke

DOI: 10.1096/FJ.02-0243FJE

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摘要: SPECIFIC AIMGlucose-dependent insulinotropic polypeptide (GIP) is secreted postprandially and acts in concert with glucose to stimulate insulin secretion from the pancreas. In type 2 diabetic patients animal models of disease where there persistent hyperglycemia, ability GIP severely abrogated due a decreased expression receptors on pancreatic β cell. Here we set out define mechanisms by which (GIPR) down-regulation could occur diabetes.PRINCIPAL FINDINGS1. Glucose down-regulates receptor concentration- time-dependent mannerGlucose (25 mM) was able significantly reduce GIPR mRNA 64 ± 7% 28 6% basal levels INS(832/13) cells after 6 24 h, respectively. Furthermore, h incubation 11 mM caused significant, 36 7%, reduction these cells. Saturation binding analyses showed marked, statistically significant decrease amount ...

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