Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou, Jiangsu, 225300, China; Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, 225001, China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Medical College, Yangzhou University, Yangzhou, 225001, China.
Peptides. 2018 Jan;99:92-98. doi: 10.1016/j.peptides.2017.11.018. Epub 2017 Dec 2.
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-1α, 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-1α/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.
我们和其他研究人员的研究结果表明，激活甘丙肽受体 1 可以通过促进大鼠骨骼肌中葡萄糖转运蛋白 4（GLUT4）的表达和转位来减轻胰岛素抵抗。但是，关于甘丙肽受体 2（GALR2）对 2 型糖尿病骨骼肌胰岛素抵抗的影响，目前尚无文献报道。在此，本研究旨在探讨 GALR2 及其信号机制在高脂肪饮食诱导肥胖小鼠中的作用。小鼠每天腹腔注射 vehicle、GALR2 激动剂 M1145 和拮抗剂 M871，连续 21 天。处理骨骼肌以测定葡萄糖摄取以及 GLUT4 mRNA 和蛋白表达水平。还定量评估了 PGC-1α、AKT、p38MAPK、AS160、pAKT、pP38MAPK 和 pAS160 的表达水平。我们发现，在高脂肪饮食方案中，GALR2 的药理学激活增强了能量消耗，并增加了小鼠骨骼肌中的 GLUT4 表达和转位。GALR2 的激活通过 P38MAPK/PGC-1α/GLUT4 和 AKT/AS160/GLUT4 途径减轻了小鼠骨骼肌中的胰岛素抵抗。总的来说，这些结果表明 GALR2 是胰岛素抵抗的调节剂，激活 GALR2 代表了一种针对肥胖引起的胰岛素抵抗的有前途的策略。
