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Albert Salehi

S Albert Salehi

Research team manager

Albert Salehi

Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction

Author

  • Jalal Taneera
  • Israa Mohammed
  • Abdul Khader Mohammed
  • Mahmood Hachim
  • Sarah Dhaiban
  • Abdullah Malek
  • Pontus Dunér
  • Noha M. Elemam
  • Nabil Sulaiman
  • Mawieh Hamad
  • Albert Salehi

Summary, in English

The expression and functional impact of most expression orphan G-protein coupled receptors (GPCRs) in β-cell is not fully understood. Microarray expression indicated that 36 orphan GPCRs are restricted in human islets, while 55 receptors overlapped between human islets and INS-1 cells. GPR183 showed higher expression in diabetic compared to non-diabetic human islets. GPR183 expression co-localized with β-cells while it was lacking in α-cells in human islets. The GPR183 agonist (7α-25-DHC) potentiated insulin secretion and protected against glucotoxicity-induced β-cell damage in human islets. Silencing of GPR183 in INS-1 cells decreased the expression of proinsulin genes, Pdx1, Mafa and impaired insulin secretion with a concomitant decrease in cAMP generation. Cultured INS-1 cells with 7α-25-DHC were associated with increased proliferation and expression of GPR183, INS2, PDX1, NeuroD, and INSR. In conclusion, the beneficial impact of GPR183 activation on β-cell function makes it a potential therapeutic target to prevent or reverse β-cell dysfunction.

Department/s

  • Diabetes - Islet Patophysiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis

Publishing year

2020

Language

English

Publication/Series

Molecular and Cellular Endocrinology

Volume

499

Document type

Journal article

Publisher

Elsevier

Topic

  • Endocrinology and Diabetes

Keywords

  • 7α-25-DHC
  • GPCRs
  • GPR183
  • Microarray gene expression
  • RNA-Sequencing
  • Type 2 diabetes

Status

Published

Research group

  • Diabetes - Islet Patophysiology
  • Cardiovascular Research - Matrix and Inflammation in Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 0303-7207