GPRC5B a putative glutamate-receptor candidate is negative modulator of insulin secretion
Författare
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.
Avdelning/ar
- Islet cell physiology
- EXODIAB: Excellence of Diabetes Research in Sweden
Publiceringsår
2013
Språk
Engelska
Sidor
643-648
Publikation/Tidskrift/Serie
Biochemical and Biophysical Research Communications
Volym
441
Issue
3
Länkar
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Biological Sciences
Nyckelord
- Diabetes
- Endocrinology
- Pancreatic islet
- Insulin secretion
- Cell
- viability
Status
Published
Forskningsgrupp
- Islet cell physiology
ISBN/ISSN/Övrigt
- ISSN: 1090-2104