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

Journal article

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 (1 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 b-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.

Authors: Soni, A; Amisten, S; Rorsman, P; Salehi, A

• Publication status: Published
• Journal: Biochemical and biophysical research communications
• Volume: 441
• Issue: 3
• Pages: 643-648
• Publication date: 2013-11-01
• DOI: 10.1016/j.bbrc.2013.10.099
• EISSN: 1090-2104
• ISSN: 0006-291X
• Language: English
• Keywords: Cell Proliferation; Insulin; Receptors, Glutamate; Down-Regulation; Aged; Female; Diabetes Mellitus, Type 2; Apoptosis; Cells, Cultured; Middle Aged; Islets of Langerhans; Insulin-Secreting Cells; Animals; Male; Humans; Adult; Receptors, G-Protein-Coupled; Mice