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

08:00 EDT 21st September 2019 | BioPortfolio

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

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.

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This article was published in the following journal.

Name: Molecular and cellular endocrinology
ISSN: 1872-8057
Pages: 110592

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Medical and Biotech [MESH] Definitions

A ubiquitously expressed G-protein-coupled receptor kinase subtype that has specificity for the agonist-occupied form of BETA-ADRENERGIC RECEPTORS and a variety of other G-PROTEIN-COUPLED RECEPTORS. Although it is highly homologous to G-PROTEIN-COUPLED RECEPTOR KINASE 2, it is not considered to play an essential role in regulating myocardial contractile response.

A family of serine-threonine kinases that are specific for G-PROTEIN-COUPLED RECEPTORS. They are regulatory proteins that play a role in G-protein-coupled receptor densensitization.

A binding partner for several RECEPTOR PROTEIN-TYROSINE KINASES, including INSULIN RECEPTOR and INSULIN-LIKE GROWTH FACTOR RECEPTOR. It contains a C-terminal SH2 DOMAIN and mediates various SIGNAL TRANSDUCTION pathways.

A DNA-binding orphan nuclear receptor that has specificity for directly repeated (DR) AGGTCA sequences. It binds DNA as either as a homodimer or as a heterodimer with the closely-related orphan nuclear receptor NUCLEAR RECEPTOR SUBFAMILY 2, GROUP C, MEMBER 2. The protein was originally identified as a PROSTATE-specific protein and is involved in the regulation of variety of cellular processes, including CELL DIFFERENTIATION; CELL PROLIFERATION; and APOPTOSIS.

An orphan nuclear receptor that has specificity for hormone response elements found in the promoters of target genes. It binds DNA either as a homodimer or as heterodimer with the closely-related orphan nuclear receptor NUCLEAR RECEPTOR SUBFAMILY 2, GROUP C, MEMBER 1. The protein was originally identified as a TESTES-specific protein and is involved in the regulation of variety of cellular processes, including CELL DIFFERENTIATION; CELL PROLIFERATION; and APOPTOSIS.

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