title: GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion.
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 (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.forename: Arvind
authors.initials: A
authors.lastname: Soni
authors.forename: Stefan
authors.initials: S
authors.lastname: Amisten
authors.forename: Patrik
authors.initials: P
authors.lastname: Rorsman
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D007515:Islets of Langerhans; D008297:Male; D051379:Mice; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000235:genetics / Q000378:metabolism
chemical_list: C410799:GPRC5B protein, human; C525103:GPRC5B receptor, mouse; D007328:Insulin; D043562:Receptors, G-Protein-Coupled; D017470:Receptors, Glutamate