游离脂肪酸受体1
葡萄糖稳态
兴奋剂
药理学
受体
内分泌学
内科学
2型糖尿病
平衡
体内
化学
医学
糖尿病
生物
胰岛素抵抗
生物技术
作者
Te Du,Liu Yang,Xu Xu,Xiaofan Shi,Xin Xu,Jian Lu,Jianlu Lv,Xi Huang,Jie Chen,Heyao Wang,Ji-Ming Ye,Lihong Hu,Xu Shen
摘要
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/Ca 2+ /IRS2/PI3K/Akt signaling pathway, while increasing glucose-stimulated insulin secretion (GSIS) by modulating GPR40/cAMP/Ca 2+ /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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