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

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GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion. / Soni, Arvind; Amisten, Stefan; Rorsman, Patrik; Salehi, S Albert.

In: Biochemical and Biophysical Research Communications, Vol. 441, No. 3, 2013, p. 643-648.

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T1 - GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion

AU - Soni, Arvind

AU - Amisten, Stefan

AU - Rorsman, Patrik

AU - Salehi, S Albert

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

KW - Diabetes

KW - Endocrinology

KW - Pancreatic islet

KW - Insulin secretion

KW - Cell

KW - viability

U2 - 10.1016/j.bbrc.2013.10.099

DO - 10.1016/j.bbrc.2013.10.099

M3 - Article

C2 - 24513213

VL - 441

SP - 643

EP - 648

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 1090-2104

IS - 3

ER -