Increased basal insulin secretion in Pdzd2-deficient mice

Molecular and Cellular Endocrinology
S W TsangK-M Yao

Abstract

Expression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet beta cells, but not in exocrine or alpha cells, suggesting a role for Pdzd2 in the regulation of pancreatic beta-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were viable and their gross morphology appeared normal. Interestingly, Pdzd2-deficient mice showed enhanced glucose tolerance in intraperitoneal glucose tolerance tests and their plasma insulin levels indicated increased basal insulin secretion after fasting. Moreover, insulin release from mutant pancreatic islets was found to be twofold higher than from normal islets. To verify the functional defect in vitro, Pdzd2 was depleted in INS-1E cells using two siRNA duplexes. Pdzd2-depleted INS-1E cells also displayed increased insulin secretion at low concentrations of glucose. Our results provide the first evidence that Pdzd2 is required for normal regulation of basal insulin secretion.

References

Jan 1, 1989·Progress in Biophysics and Molecular Biology·F M Ashcroft, P Rorsman
May 13, 1997·Proceedings of the National Academy of Sciences of the United States of America·M BaierR Kurth
Apr 28, 1997·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·T NagaseO Ohara
Nov 24, 1999·Molecular and Cellular Biology·M K ThomasJ F Habener
Dec 7, 2002·Diabetes/metabolism Research and Reviews·Susanne G Straub, Geoffrey W G Sharp
Dec 18, 2002·Proceedings of the National Academy of Sciences of the United States of America·J C KosterC G Nichols
Apr 24, 2003·Science's STKE : Signal Transduction Knowledge Environment·Claire NourryJean-Paul Borg
Sep 21, 2004·Nature Reviews. Neuroscience·Eunjoon Kim, Morgan Sheng
Aug 3, 2005·The Journal of Clinical Investigation·Frances M Ashcroft
Oct 27, 2005·Diabetes·Joseph C KosterColin G Nichols
Dec 3, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Patrick E MacDonaldPatrik Rorsman
Jan 18, 2006·The International Journal of Biochemistry & Cell Biology·Richard Yam Man MaKwok-Ming Yao
Aug 4, 2006·Biochimica Et Biophysica Acta·Pascale Zimmermann
Jul 21, 2007·Science·Michael A StifflerGavin MacBeath

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