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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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