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

Summary, in English

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.

• Author: Arvind Soni; Stefan Amisten; Patrik Rorsman; S Albert Salehi
• Department/s: Islet cell physiology; EXODIAB: Excellence of Diabetes Research in Sweden
• Publishing year: 2013
• Language: English
• Pages: 643-648
• Publication/Series: Biochemical and Biophysical Research Communications
• Volume: 441
• Issue: 3
• Links: http://www.ncbi.nlm.nih.gov/pubmed/24513213?dopt=Abstract; http://dx.doi.org/10.1016/j.bbrc.2013.10.099
• Document type: Journal article
• Publisher: Elsevier
• Topic: Biological Sciences
• Keywords: Diabetes; Endocrinology; Pancreatic islet; Insulin secretion; Cell; viability
• Status: Published
• Research group: Islet cell physiology
• ISBN/ISSN/Other: ISSN: 1090-2104