The effect and mechanism of N-(Z)-9-octadecenyl-2-propanesulfonamide in treatment of insulin resistance in type 2 diabetic mice
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(S; TZ)连续小剂量腹腔注射诱导T2DM小鼠模型, N15(50、100和200 mg·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; 。This study was designed to investigate the therapeutic effect and; mechanisms of action of novel compound; N-(Z)-9-octadecenyl-2-propanesulfonamide(N15) on type 2 diabetes(T2DM).; A mouse model of T2DM was established with multiple injection of; streptozotocin(STZ) at a low dose. N15 at different doses(50, 100 and; 200 mg·kg~(-1)·d~(-1)) and pioglitazone(6 mg·kg~(-1)·d~(-1)) were; administrated orally for 6 weeks. The level of fasting blood; glucose(FBG) and fasting insulin(FIns) were measured in the course of; the experiment for insulin resistance index(HOMA-IR). Oral glucose; tolerance test(OGTT) and intraperitoneal insulin tolerance test(IPITT); were determined in the treated mice. The expression of Akt, AMPK and; Glut4 in liver were analyzed by Western blot. N15 was found to reduce; the level of FBG, FIns and HOMA-IR(P < 0.01) and ameliorate the glucose; and insulin tolerance(P < 0.01, P < 0.001). Simultaneously the protein; expression of p-Akt, p-AMPK and Glut4 was significantly increased in; liver by N15(P < 0.01). These effects were similar to those of; pioglitazone(P > 0.05). These results suggested that the novel compound; N15 can ameliorate insulin resistance and the potential mechanism may be; associated with increased insulin signaling in liver and promotion of; phosphatidyl inositol 3 phosphate phosphorylation.