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

Abstract

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 glucose-stimulated 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.

• Authors: 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
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 240 Issue 2 Pg. 195-214 (02 01 2019) ISSN: 1479-6805 [Electronic] England
• PMID: 30400036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Ffar1 protein, mouse
• Receptors, G-Protein-Coupled
• Vasodilator Agents
• Vincamine
• Glucose

Topics

• Animals
• Blood Glucose (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Diabetes Mellitus, Experimental (genetics, metabolism, prevention & control)
• Diabetes Mellitus, Type 2 (genetics, metabolism, prevention & control)
• Glucose (metabolism)
• Homeostasis (drug effects)
• Insulin Secretion (drug effects)
• Insulin-Secreting Cells (drug effects, metabolism)
• Male
• Mice
• Receptors, G-Protein-Coupled (agonists, genetics, metabolism)
• Signal Transduction (drug effects)
• Vasodilator Agents (pharmacology)
• Vincamine (pharmacology)