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

Taneera, Jalal, Mohammed, Israa, Mohammed, Abdul Khader, Hachim, Mahmood, Dhaiban, Sarah, Malek, Abdullah, Dunér, Pontus, Elemam, Noha M., Sulaiman, Nabil, Hamad, Mawieh, Salehi, Albert
Molecular and cellular endocrinology 2020 v.499
G-protein coupled receptors, G-proteins, agonists, cyclic AMP, genes, humans, insulin secretion, islets of Langerhans, microarray technology, proinsulin, therapeutics
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.