Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice.

Autor: Te Du, Liu Yang, Xu Xu, Xiaofan Shi, Xin Xu, Jian Lu, Jianlu Lv, Xi Huang, Jing Chen, Heyao Wang, Jiming Ye, Lihong Hu, Xu Shen
Předmět:
Zdroj: Journal of Endocrinology; Feb2019, Vol. 240 Issue 2, p195-214, 20p
Abstrakt: 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 β-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting β-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 GP R40 and its potential in the treatment of T2DM. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index