期刊
JOURNAL OF ENDOCRINOLOGY
卷 240, 期 2, 页码 195-214出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-18-0432
关键词
vincamine; GPR40; beta-cell function; insulin secretion; type 2 diabetes
资金
- National Natural Science Foundation of China [81473141, 81773596]
- NSFC-TRF collaboration project [NSFC81561148011]
- Key Laboratory of Receptor Research of the Chinese Academy of Sciences [SIMM1606YZZ-04]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (Integration of Chinese and Western Medicine)
Vincamine, a monoterpenoid indole alkaloid extracted from the Madagascar periwinkle, is clinically used for the treatment of cardio-cerebrovascular diseases, while also treated as a dietary supplement with nootropic function. Given the neuronal protection of vincamine and the potency of beta-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting it-cells and ameliorating glucose homeostasis in vitro and in vivo. Interestingly, we found that vincamine could protect INS-832/13 cells function by regulating G-protein-coupled receptor 40 (GPR40)/cAMP/Ca2+/IRS2/PI3K/Akt signaling pathway, while increasing glucosestimulated insulin secretion (GSIS) by modulating GPR40/cAMP/Ca2+/CaMKII pathway, which reveals a novel mechanism underlying GPR40-mediated cell protection and GSIS in INS-832/13 cells. Moreover, administration of vincamine effectively ameliorated glucose homeostasis in either HFD/STZ or db/db type 2 diabetic mice. To our knowledge, our current work might be the first report on vincamine targeting GPR40 and its potential in the treatment of T2DM.
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