Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice
Activiated galanin receptor 2 attenuates insulin resistance in skeletal muscle of obese mice
复制标题
激活的甘丙肽受体2可减弱肥胖小鼠骨骼肌的胰岛素抵抗
DOI：
10.1016/j.peptides.2017.11.018
复制
发表时间：
2018-01-01
期刊：
影响因子：
3
通讯作者：
Bo, Ping
中科院分区：
文献类型：
--
作者：
Fang, Penghua;Zhang, Lei;Bo, Ping
本课题组及其他研究结果表明，甘丙肽受体1的激活可通过促进大鼠骨骼肌葡萄糖转运蛋白4（GLUT 4）的表达和转位来减轻胰岛素抵抗。但甘丙肽受体2（GALR 2）在2型糖尿病骨骼肌胰岛素抵抗中的作用尚未见报道。本研究旨在探讨GALR 2在高脂饮食诱导的肥胖小鼠中的作用及其信号机制。小鼠分别腹腔注射溶媒、GALR 2激动剂M1145和拮抗剂M871，每天1次，连续21天。处理骨骼肌以测定葡萄糖摄取以及GLUT 4 mRNA和蛋白表达水平。定量检测PGC-1 α、AKT、p38 MAPK、AS 160、pAKT、pP 38 MAPK和pAS 160的表达水平。我们发现，药理学激活GALR 2增强能量消耗，并增加GLUT 4的表达和易位在高脂饮食方案的小鼠骨骼肌。GALR 2的激活通过P38 MAPK/PGC-1 α/GLUT 4和AKT/AS 160/GLUT 4途径减轻小鼠骨骼肌的胰岛素抵抗。总体而言，这些结果确定GALR 2是胰岛素抵抗的调节剂，并且GALR 2的激活代表了对抗肥胖诱导的胰岛素抵抗的有希望的策略。
The results of our and other's studies showed that activation of galanin receptor 1 could mitigate insulin resistance via promoting glucose transporter 4 (GLUT4) expression and translocation in the skeletal muscle of rats. But no literature are available regarding the effect of galanin receptor 2 (GALR2) on insulin resistance in skeletal muscle of type 2 diabetes. Herein, in this study we intended to survey the effect of GALR2 and its signal mechanisms in the mice with high fat diet-induced obese. The mice were intraperitoneally injected with vehicle, GALR2 agonist M1145 and antagonist M871 respectively once a day for continuous 21 days. The skeletal muscles were processed for determination of glucose uptake, and GLUT4 mRNA and protein expression levels. The PGC-1 alpha, AKT, p38MAPK, AS160, pAKT, pP38MAPK and pAS160 expression levels were quantitatively assessed too. We found that pharmacological activation of GALR2 enhanced energy expenditure, and increased GLUT4 expression and translocation in skeletal muscle of mice during high-fat diet regimens. Activation of GALR2 alleviated insulin resistance through P38MAPK/PGC-1 alpha/GLUT4 and AKT/AS160/GLUT4 pathway in the skeletal muscle of mice. Overall, these results identify that GALR2 is a regulator of insulin resistance and activation of GALR2 represents a promising strategy against obesity-induced insulin resistance.