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

  • J Endocrinol. 2019 Feb 1;240(2):195-214. doi: 10.1530/JOE-18-0432.
Te Du  1  2 ,  Liu Yang  1  2 ,  Xu Xu  3 ,  Xiaofan Shi  1  2 ,  Xin Xu  1  2 ,  Jian Lu  3 ,  Jianlu Lv  3 ,  Xi Huang  3 ,  Jing Chen  1  2 ,  Heyao Wang  1  2 ,  Jiming Ye  4 ,  Lihong Hu  3 ,  Xu Shen  1  2  3
Affiliations
  • 1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
  • 2. School of Pharmacy, University of Chinese Academy of Sciences, Beijing, China.
  • 3. School of Medicine and Life Sciences, Nanjing University of Chinese Medicine, Nanjing, China.
  • 4. School of Health and Biomedical Sciences, RMIT University, Victoria, Australia.
PMID: 30400036 DOI: 10.1530/JOE-18-0432
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.

Keywords
GPR40; insulin secretion; type 2 diabetes; vincamine; β-cell function.
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