Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction
(2020) In Molecular and Cellular Endocrinology 499.- Abstract
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... (More)
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.
(Less)
- author
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- 7α-25-DHC, GPCRs, GPR183, Microarray gene expression, RNA-Sequencing, Type 2 diabetes
- in
- Molecular and Cellular Endocrinology
- volume
- 499
- article number
- 110592
- publisher
- Elsevier
- external identifiers
-
- scopus:85072519410
- pmid:31550518
- ISSN
- 0303-7207
- DOI
- 10.1016/j.mce.2019.110592
- language
- English
- LU publication?
- yes
- id
- 9b8251a9-dd33-4b84-873a-5e98cf90a456
- date added to LUP
- 2021-01-15 10:38:06
- date last changed
- 2024-10-03 17:12:47
@article{9b8251a9-dd33-4b84-873a-5e98cf90a456, abstract = {{<p>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.</p>}}, author = {{Taneera, Jalal and Mohammed, Israa and Mohammed, Abdul Khader and Hachim, Mahmood and Dhaiban, Sarah and Malek, Abdullah and Dunér, Pontus and Elemam, Noha M. and Sulaiman, Nabil and Hamad, Mawieh and Salehi, Albert}}, issn = {{0303-7207}}, keywords = {{7α-25-DHC; GPCRs; GPR183; Microarray gene expression; RNA-Sequencing; Type 2 diabetes}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Molecular and Cellular Endocrinology}}, title = {{Orphan G-protein coupled receptor 183 (GPR183) potentiates insulin secretion and prevents glucotoxicity-induced β-cell dysfunction}}, url = {{http://dx.doi.org/10.1016/j.mce.2019.110592}}, doi = {{10.1016/j.mce.2019.110592}}, volume = {{499}}, year = {{2020}}, }