SGK1 抑制剂改善糖代谢紊乱的作用研究

目的:观察血清和糖皮质激素诱导的蛋白激酶1(serum and glucocorticoid-induced protein kinase1,SGK1)抑制剂对db/db小鼠糖代谢紊乱的改善作用,初步探讨该作用是否与改善脂肪组织功能紊乱有关。方法:将db/db小鼠随机分为db/db组、抑制剂组,同时设db/m组,db/db组、db/m组小鼠给予普通饲料喂养,抑制剂组小鼠给予含SGK1抑制剂的饲料喂养,干预8周。观察体重、摄食量、空腹血糖(fasting blood glucose,FBG)、糖化血红蛋白(glycosylated hemoglobin,Hb A1C),干预8周后行腹腔葡萄糖耐量试验(intraperitoneal glucose tolerance test,IPGTT)、腹腔胰岛素耐量试验(intraperitoneal insulin tolerance test,IPITT)。酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测血清空腹胰岛素(fasting insulin,FINS)水平,计算胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)及胰岛素敏感性指数(insulin sensitivity index,ISI)。实时定量荧光PCR(real-time PCR)法检测脂肪组织中SGK1、脂肪细胞因子m RNA表达水平。结果:干预8周后,抑制剂组体重、FBG、Hb A1C、IPGTT、IPITT均低于db/db组(P0.05),摄食量无明显差异。与db/db组相比,抑制剂组血清FINS有下降趋势,HOMA-IR明显降低,ISI明显升高(P0.05)。SGK1抑制剂干预治疗后,脂肪组织中SGK1、单核细胞趋化因子-1(monocyte chemotactic protein-1,MCP-1)、凝血酶元激活因子的抑制因子-1(plasminogen activator inhibitor 1,PAI-1)m RNA表达下降(P0.05),脂联素(adiponectin)m RNA表达无明显变化。结论:SGK1抑制剂干预治疗可一定程度改善db/db小鼠糖代谢紊乱,该作用可能部分与改善脂肪组织功能紊乱有关。

Effect of SGK1 Inhibitor on Improving Glucose MetabolismDisorders

Objective:To investigate the treatment effect of SGK1 inhibitor on improving glucose metabolism disorders in db/db mice, and to explore whether the possible mechanism is due to the effect of improving the adipose tissue dysfunction.Methods:The db/db mice were randomly divided into db/db group, inhibitor group, at the same time set up the db/m group. The mice of db/db group and db/m group were fed with ordinary diet, and the mice of inhibitor group were received the diet containing SGK1 inhibitor. The intervention lasted for 8 weeks. During the intervention period, the body weight, food intake, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1C) were investigated. After the intervention, intraperitoneal glucose tolerance test (IPGTT) and intraperitoneal insulin tolerance test (IPITT) were conducted. The expression levels of the fasting insulin (FINS) were detected in the blood serum by enzyme linked immunosorbent assay(ELISA) method. The mRNA expression levels of SGK1 and adipokines were detected in the adipose tissues by quantitative real-time PCR.Results:After 8 week treatment, the body weight, FBG, HbA1C, IPGTT, IPITT were lower in the inhibitor group than that in the db/db group (P<0.05). The food intake between the two groups had no statistical difference. Compared with db/db group, the mice in inhibitor group had lower serum FINS, significantly decreased HOMA-IR and increased ISI (P<0.05). After the intervention of SGK1 inhibitor, the mRNA expression levels of SGK1, MCP-1 and PAI-1 in adipose tissues were decreased (P<0.05), the mRNA expression levels of adiponectin did not change significantly.Conclusion:SGK1 inhibitor treatment can significantly improve hyperglycemia in db/db mice, and its possible mechanismmay be partially due to its effect of improving adipose dysfunction.