摘要
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。
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（P0.01）and ameliorate the glucose and insulin tolerance（P0.01,P0.001）.Simultaneously the protein expression of p-Akt,p-AMPK and Glut4 was significantly increased in liver by N15（P0.01）.These effects were similar to those of pioglitazone（P0.05）.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.
出处
《药学学报》
CAS
CSCD
北大核心
2017年第12期1871-1876,共6页
Acta Pharmaceutica Sinica
基金
国家自然基金联合基金
促进海峡两岸科技合作联合基金项目(U1405215)
泉州市科技计划项目"细胞组织资源库"(2016Z006)
泉州市科技计划项目"泉州市生物与新医药产业转型升级发展规划研究"(2016Z075)
