• Yukihiro Fujita, Rhonda D Wideman, Ali Asadi, Gary K Yang, Robert Baker, Travis Webber, Tianjiao Zhang, Rennian Wang, Ziliang Ao, Garth L Warnock, Yin Nam Kwok, and Timothy J Kieffer.
• Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.
• Gastroenterology. 2010 May 1; 138 (5): 1966-75.

Background & AimsGlucose-dependent insulinotropic polypeptide (GIP) and the proglucagon product glucagon-like peptide-1 (GLP-1) are gastrointestinal hormones that are released in response to nutrient intake and promote insulin secretion. Interestingly, a subset of enteroendocrine cells express both GIP and GLP-1. We sought to determine whether GIP also might be co-expressed with proglucagon in pancreatic alpha-cells.MethodsWe assessed GIP expression via reverse-transcription polymerase chain reaction, in situ hybridization, and immunohistochemistry. We developed a novel bioassay to measure GIP release from isolated islets, compared the biological activities of full-length and truncated GIP, and assessed the impact of immunoneutralization of islet GIP on glucose-stimulated insulin secretion in isolated islets.ResultsGIP messenger RNA was present in mouse islets; GIP protein localized to islet alpha-cells of mouse, human, and snake pancreas, based on immunohistochemical analyses. However, using a C-terminal GIP antibody, immunoreactivity was detected in islets from prohormone convertase (PC) 2 knockout but not wild-type mice. Bioactive GIP was secreted from mouse and human islets after arginine stimulation. In the perfused mouse pancreas, GIP(1-42) and amidated GIP(1-30) had equipotent insulinotropic actions. Finally, immunoneutralization of GIP secreted by isolated islets decreased glucose-stimulated insulin secretion.ConclusionsGIP is expressed in and secreted from pancreatic islets; in alpha-cells, PC2 processes proGIP to yield a truncated but bioactive form of GIP that differs from the PC1/3-derived form from K-cells. Islet-derived GIP promotes islet glucose competence and also could support islet development and/or survival.Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

43 keywords...

hide…