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Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells
Vong,Chi Teng1; Tseng,Hisa Hui Ling1; Kwan,Yiu Wa2; Lee,Simon Ming Yuen1; Hoi,Maggie Pui Man1
2019-03-01
Source PublicationBiomedicine and Pharmacotherapy
ISSN0753-3322
Volume111Pages:1176-1186
AbstractInsulin resistance and β-cell dysfunction are the main defects in Type 2 Diabetes Mellitus (T2DM), and β-cell dysfunction and apoptosis is the critical determinant in the progression of T2DM. G-protein coupled receptor 55 (GPR55) is an orphan G-protein coupled receptor, which is activated by endocannabinoids and lipid transmitters. Recently, GPR55 was shown to regulate glucose and energy homeostasis, however its role in β-cell apoptosis was not studied. Therefore, in this study, we investigated the novel effect of GPR55 agonists, O-1602 and abnormal cannabidiol (Abn-CBD), on endoplasmic reticulum (ER) stress-induced apoptosis in mouse pancreatic β-cell lines, MIN6 and Beta-TC-6, and its underlying mechanisms. Our results showed that O-1602 and Abn-CBD reduced ER stress-induced apoptosis in MIN6 and Beta-TC-6 cells. This was through the phosphorylation of 3′-5′-cyclic adenosine monophosphate response element-binding protein (CREB) in β-cells, hence activating CREB downstream anti-apoptotic genes, Bcl-2 and Bcl-xL. Moreover, O-1602 and Abn-CBD directly activated kinases, CaMKIV, Erk1/2 and PKA, to induce CREB phosphorylation. Therefore, our results indicated that GPR55 agonists protected from β-cell apoptosis through CREB activation, thus up-regulating anti-apoptotic genes. In conclusion, our study provided a novel protective effect of GPR55 agonists on ER stress-induced apoptosis in β-cells and its underlying mechanisms mediating this protection, therefore we suggested that GPR55 might be a therapeutic target for T2DM.
KeywordCREB ER stress GPR55 β-Cell apoptosis
DOI10.1016/j.biopha.2018.12.126
URLView the original
Language英语
Scopus ID2-s2.0-85059847834
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Cited Times [WOS]:7   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorHoi,Maggie Pui Man
Affiliation1.State Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macau,Taipa,Avenida da Universidade,China
2.School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Shatin,Hong Kong
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Vong,Chi Teng,Tseng,Hisa Hui Ling,Kwan,Yiu Wa,et al. Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells[J]. Biomedicine and Pharmacotherapy,2019,111:1176-1186.
APA Vong,Chi Teng,Tseng,Hisa Hui Ling,Kwan,Yiu Wa,Lee,Simon Ming Yuen,&Hoi,Maggie Pui Man.(2019).Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells.Biomedicine and Pharmacotherapy,111,1176-1186.
MLA Vong,Chi Teng,et al."Novel protective effect of O-1602 and abnormal cannabidiol, GPR55 agonists, on ER stress-induced apoptosis in pancreatic β-cells".Biomedicine and Pharmacotherapy 111(2019):1176-1186.
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