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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.