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探索新化合物N-(Z)-9-十八烯基-2-丙磺酰胺(N15)对2型糖尿病(T2DM)胰岛素抵抗小鼠的影响并探讨其可能作用机制。采用链脲佐菌素(STZ)连续小剂量腹腔注射诱导T2DM小鼠模型,N15(50、100和200mg·kg~(-1)·d~(-1))和吡格列酮(6 mg·kg~(-1)·d~(-1))连续灌胃给药6周,期间分别对小鼠空腹血糖(FBG)、胰岛素(FIns)和胰岛素抵抗指数(HOMA-IR)进行测定比较;并于末次给药后测定各组小鼠葡萄糖耐量(OGTT)和胰岛素耐量(IPITT);通过Western blot对能量代谢关键蛋白Akt、AMPK和Glut4加以分析。结果表明,N15可显著降低模型小鼠FBG、Fins和HOMA-IR水平(P<0.01),改善葡萄糖及胰岛素耐受程度(P<0.01,P<0.001),并显著上调肝脏p-Akt、p-AMPK和Glut4蛋白表达水平(P<0.01),且作用效果与吡格列酮相当(P>0.05)。上述结果表明,新型化合物N15具有改善2型糖尿病胰岛素抵抗的功效,其机制可能与增加肝内胰岛素受体调节及促使磷脂酰肌醇3磷酸磷酸化相关。
To investigate the effect of a new compound N- (Z) -9-octadecenyl-2-propanesulfonamide (N15) on type 2 diabetes mellitus (T2DM) insulin resistance in mice and to explore its possible mechanism. T2DM mice were induced by continuous small dose of streptozotocin (STZ), and were induced by N15 (50, 100 and 200 mg · kg -1 · d -1) and pioglitazone (6 mg · kg ~ (-1) · d -1) for 6 weeks. The fasting blood glucose (FBG), insulin (FIns) and insulin resistance index (HOMA-IR) After the last administration, the glucose tolerance (OGTT) and insulin tolerance (IPITT) of mice in each group were measured. The key proteins of energy metabolism, Akt, AMPK and Glut4, were analyzed by Western blot. The results showed that N15 could significantly decrease the levels of FBG, Fins and HOMA-IR (P <0.01), improve the tolerance of glucose and insulin (P <0.01, P <0.001) -AMPK and Glut4 protein levels (P <0.01), and the effect was similar to that of pioglitazone (P> 0.05). The above results show that the new compound N15 has the effect of improving insulin resistance of type 2 diabetes mellitus, and its mechanism may be related to increasing intrahepatic insulin receptor regulation and promoting phosphatidylinositol 3 phosphate phosphorylation.