GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion

Research output: Contribution to journalArticle

Abstract

GPRC5B is an orphan receptor belonging to the group C family of G protein-coupled receptors (GPCRs). GPRC5B is abundantly expressed in both human and mouse pancreatic islets, and both GPRC5B mRNA and protein are up-regulated 2.5-fold in islets from organ donors with type 2 diabetes. Expression of Gprc5b is 50% lower in islets isolated from newborn (<3 weeks) than in adult (>36 weeks) mice. Lentiviral shRNA-mediated down-regulation of Gprc5b in intact islets from 12 to 16 week-old mice strongly (2.5-fold) increased basal (I mmol/l) and moderately (40%) potentiated glucose (20 mmol/l) stimulated insulin secretion and also enhanced the potentiating effect of glutamate on insulin secretion. Downregulation of Gprc5b protected murine insulin-secreting clonal MIN6 cells against cytokine-induced apoptosis. We propose that increased expression of GPRC5B contributes to the reduced insulin secretion and beta-cell viability observed in type-2 diabetes. Thus, pharmacological targeting of GPRC5B might provide a novel means therapy for the treatment and prevention of type-2 diabetes. (C) 2013 Elsevier Inc. All rights reserved.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences

Keywords

  • Diabetes, Endocrinology, Pancreatic islet, Insulin secretion, Cell, viability
Original languageEnglish
Pages (from-to)643-648
JournalBiochemical and Biophysical Research Communications
Volume441
Issue number3
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes