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

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

doi:10.1016/j.mce.2019.110592

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

Mol Cell Endocrinol. 2020 Jan 1:499:110592. doi: 10.1016/j.mce.2019.110592. Epub 2019 Sep 21.

Authors

Affiliations

¹ Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates. Electronic address: jtaneera@sharjah.ac.ae.
² Department of Clinical Science, UMAS, Clinical Research Center, Lund University, Malmö, Sweden.
³ Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates.
⁴ Department of Basic Medical Sciences, College of Medicine, University of Sharjah, Sharjah, United Arab Emirates.
⁵ Sharjah Institute for Medical Research, University of Sharjah, Sharjah, United Arab Emirates; Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
⁶ Department of Clinical Science, UMAS, Clinical Research Center, Lund University, Malmö, Sweden; Department of Neuroscience and Physiology, Metabolic Research Unit, University of Gothenburg, Gothenburg, Sweden. Electronic address: s_albert.salehi@med.lu.se.

PMID: 31550518
DOI: 10.1016/j.mce.2019.110592

Abstract

The expression and functional impact of most 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.

Keywords: 7α-25-DHC; GPCRs; GPR183; Microarray gene expression; RNA-Sequencing; Type 2 diabetes.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
Diabetes Mellitus, Type 2 / genetics
Diabetes Mellitus, Type 2 / metabolism*
Female
Gene Expression Profiling
Humans
Hydroxycholesterols / pharmacology*
Insulin Secretion
Insulin-Secreting Cells / cytology*
Insulin-Secreting Cells / metabolism
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Receptors, G-Protein-Coupled / genetics*
Receptors, G-Protein-Coupled / metabolism*
Signal Transduction

Substances

GPR183 protein, human
Hydroxycholesterols
Receptors, G-Protein-Coupled