Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice
Vincamine as a GPR40 agonist improves glucose homeostasis in type 2 diabetic mice
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长春胺作为 GPR40 激动剂可改善 2 型糖尿病小鼠的葡萄糖稳态
DOI：
10.1530/joe-18-0432
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发表时间：
2019-02-01
影响因子：
4
通讯作者：
Shen, Xu
中科院分区：
文献类型：
--
作者：
Du, Te;Yang, Liu;Shen, Xu
藜芦胺是从马达加斯加长春花中提取的一种单萜类吲哚生物碱，临床上用于治疗心脑血管疾病，同时也作为一种具有益智功能的膳食补充剂。鉴于长春胺的神经元保护作用和β细胞改善治疗2型糖尿病（T2 DM）的潜力，我们研究了长春胺在体外和体内保护β细胞和改善葡萄糖稳态的潜力。有趣的是，我们发现长春胺可以通过调节G蛋白偶联受体40（GPR 40）/cAMP/Ca 2 +/IRS 2/PI 3 K/Akt信号通路来保护INS-832/13细胞的功能，同时通过调节GPR 40/cAMP/Ca 2 +/CaMKII信号通路来增加葡萄糖估计的胰岛素分泌（GSIS），这揭示了GPR 40介导的INS-832/13细胞保护和GSIS的新机制。此外，长春胺的施用有效地改善了HFD/STZ或db/db 2型糖尿病小鼠中的葡萄糖稳态。据我们所知，我们目前的工作可能是第一次报道长春胺靶向GPR 40及其在治疗T2 DM中的潜力。
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 beta-cell amelioration in treating type 2 diabetes mellitus (T2DM), we investigated the potential of vincamine in protecting it-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 GPR40 and its potential in the treatment of T2DM.