Increased basal insulin secretion in Pdzd2-deficient mice.

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.

journal_name

Mol Cell Endocrinol

authors

Tsang SW,Shao D,Cheah KS,Okuse K,Leung PS,Yao KM

doi

10.1016/j.mce.2009.11.007

subject

Has Abstract

pub_date

2010-02-05 00:00:00

pages

263-70

issue

1-2

eissn

0303-7207

issn

1872-8057

pii

S0303-7207(09)00572-3

journal_volume

315

pub_type

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