G-protein coupled receptor 55 agonists increase insulin secretion through inositol trisphosphate-mediated calcium release in pancreatic β-cells
Publication in refereed journal

香港中文大學研究人員
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其它資訊
摘要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 play a role in glucose and energy homeostasis, and insulin secretion is essential to maintain glucose homeostasis in the body. In Type 2 Diabetes Mellitus (T2DM), chronic insulin resistance and a progressive decline in β-cell function result in β-cell dysfunction, this leads to defect in insulin secretion, which is the key process in the development and progression of T2DM. GPR55 agonists were shown to increase insulin secretion, however the underlying mechanisms were not fully understood. Therefore the aim of the present study was to examine the effects of potent GPR55 agonists, O-1602 and abnormal cannabidiol (Abn-CBD), on glucose-induced insulin secretion in a mouse pancreatic β-cell line, MIN6, and the underlying mechanisms with a focus on intracellular calcium (Ca2+). Our results demonstrated that O-1602 and Abn-CBD increased glucose-induced insulin secretion in MIN6 cells, which was abolished by a PLC inhibitor, U73122. Glucose-induced Ca2+ transients were enhanced by O-1602 and Abn-CBD, and this was significantly reduced by U73122 and inositol trisphosphate (IP3) receptor inhibitors, 2-aminoethoxydiphenyl borate (2-APB) and xestospongin C, as well as by Y-27632, a Rho-associated protein kinase (ROCK) inhibitor. Interestingly, O-1602 and Abn-CBD could directly induce intracellular Ca2+ transients through IP3-mediated Ca2+ release. In conclusion, GPR55 agonists increased insulin secretion through calcium mobilisation from IP3-sensitive ER stores in β-cells.
著者Chi Teng VONG, Hisa Hui Ling TSENG,, Yiu Wa KWAN, Simon Ming-Yuen LEE, Maggie Pui Man HOI
期刊名稱European Journal of Pharmacology
出版年份2019
月份7
日期5
卷號854
出版社Elsevier: 12 months
頁次372 - 379
國際標準期刊號0014-2999
語言英式英語

上次更新時間 2020-12-09 於 03:38