壳寡糖胍对胰岛素抵抗及相关蛋白的作用

Effects of Chitooligosaccharide Guanidine on Insulin Resistance and Related Protein

针对壳寡糖胍(COSG)对动物体内胰岛素抵抗治疗效果及相关机制尚不明确的问题,建立高脂高糖饮食联合链脲佐菌素诱导的2型糖尿病(T2DM)大鼠模型,并进行COSG灌胃给药治疗8周,研究COSG对T2DM大鼠体内胰岛素抵抗及相关信号通路的影响.结果显示,COSG可明显降低T2DM大鼠血清中总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)水平并提高血清中高密度脂蛋白(HDL)水平;此外,COSG可下调T2DM大鼠的空腹血糖(FBG)和空腹胰岛素(FINS)含量,并减小T2DM大鼠胰岛素抵抗指数(HOMA-IR).进一步研究相关蛋白发现,COSG可抑制骨骼肌中p38丝裂原活化蛋白激酶(p38 MAPK)的磷酸化以及提高胰岛素受体底物-1(IRS-1)酪氨酸位点的磷酸化,并提高蛋白激酶B(AKT)的磷酸化水平和促进葡萄糖转运蛋白4(GLUT4)转移至细胞膜,从而促进细胞对葡萄糖的摄取;另外,COSG还可以降低磷酸烯醇式丙酮酸羧激酶(PEPCK)和肌糖原水平,进而抑制糖异生.从而,COSG达到改善胰岛素抵抗的作用.总之,COSG可改善T2DM大鼠胰岛素抵抗,具有良好的应用前景.

The effects of chitooligosaccharide guanidine(COSG)on insulin resistance and its related in vivo mechanisms still remain unclear.Therefore,in this study,a type 2 diabetic(T2DM)rat model was established using a highfat and high-sugar diet combined with streptozotocin,followed by intragastric administration of COSG for 8 weeks,to investigate the effects of COSG on insulin resistance and the related signaling pathways in T2DM rats.Results demonstrated that COSG significantly reduced the levels of total cholesterol(TC),triglycerides(TGs),and low-density lipoprotein(LDL)and increased the levels of high-density lipoprotein(HDL)in the serum of T2DM rats.Furthermore,COSG downregulated the levels of fasting blood glucose(FBG)and fasting insulin(FINS)and decreased the homeostatic model assessment for insulin resistance(HOMA-IR)index in T2DM rats.Further analysis of related proteins showed that COSG inhibited the phosphorylation of p38 mitogen-activated protein kinase(p38 MAPK),increased the tyrosine phosphorylation of insulin receptor substrate-1(IRS-1)proteins,increased the phosphorylation of protein kinase B(Akt),and promoted the transfer of GLUT4 to the cell membrane,thereby promoting the uptake of glucose by cells.Results also showed that COSG can reduce the levels of phosphoenolpyruvate carboxykinase(PEPCK)and muscle glycogen,thereby inhibiting gluconeogenesis.Therefore,COSG has the effect of improving insulin resistance.In conclusion,COSG can improve insulin resistance in T2DM rats,a finding that has a good application prospect.