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胃转流术对2型糖尿病大鼠肝细胞磷酸烯醇丙酮酸羧激酶表达的影响

Hepatic phosphoenolpyruvate carboxykinase expression after gastric bypass surgery in rats with type 2 diabetes mellitus
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摘要 目的观察胃转流术(gastric bypass,GBS)对自发性2型糖尿病大鼠(GK大鼠)肝细胞磷酸烯醇丙酮酸羧激酶(PEPCK)mRNA及其蛋白表达的影响,探讨其改善胰岛素抵抗的机制。方法36只12周龄雄性GK大鼠采用随机数字法分为GBS手术组、假手术组、SO饮食配对组,每组12只。检测和比较术前及术后8周各组大鼠血脂水平和空腹血糖(FPG)水平,对胰岛素敏感指数(ISI)进行计算。应用实时聚合酶链反应(RT-PCR)与蛋白印迹(Westernblot)技术检测各组术后8周肝细胞PEPCKmRNA及其蛋白的表达。结果术后8周,GBS手术组的血脂水平[TC(1.25±0.08)mmol/L,TG(0.93±0.10)mmol/L,FFA(0.88±0.12)mmol/L]较术前[TC(2.31±0.52)mmol/L,TG(1.44±0.27)mmol/L,FFA(1.08±0.06)mmol/L]显著降低,差异有统计学意义(P<0.05);GBS手术组FPG水平由术前的(11.73±0.37)mmol/L下降至(5.13±0.22)mmol/L,差异有统计学意义(P<0.05);GBS手术组ISI由术前的(-5.78±0.10)上升至(-4.64±0.15),差异有统计学意义(P<0.05);PEPCK的mRNA(3.97±0.30)和蛋白(1.60±0.31)表达相比术前明显减少,差异有统计学意义(P<0.05)。结论GBS可降低T2DM大鼠血糖,同时改善糖耐量,胰岛素抵抗症状。其机制似乎与肝细胞内PEPCKmRNA和蛋白表达的下降有关。 Objective To investigate mRNA expression of hepatic phosphoenolpyruvate carboxykinase (PEPCK) after gastric bypass surgery (GBS) in rats with type 2 diabetes mellitus (T2DM) . Methods 36 male Goto-Kakizaki rats, aged 12 weeks, were randomly divided into GBS, sham operation with diet restriction (SO) , and sham operation alone (control) groups (n=12 per group) . The blood lipid levels and fasting plasma glucose (FPG) levels in rats before and 8 weeks after surgery were measured and compared. The insulin sensitivity index (ISI) was calculated. Real-time polymerase chain reaction (RT-PCR) and Western blot were used to detect the expression of PEPCK mRNA and protein in hepatocytes at 8 weeks after operation. Results 8 weeks after operation, the blood lipid levels [TC (1.25±0.08) mmol/L, TG (0.93±0.10) mmol/L, FFA (0.88±0.12) mmol/L] in GBS group were significantly lower than those before operation [TC (2.31±0.52) mmol/L, TG (1.44±0.27) mmol/L,FFA (1.08±0.06) mmol/L] (P<0.05) .The fasting blood glucose levels in GBS decreased from (11.73±0.37) mmol/L to (5.13±0.22) mmol/L (P<0.05) , and ISI in GBS group increased from (-5.78±0.10) to (-4.64±0.15) (P<0.05) . PEPCKmRNA (3.97±0.30) and protein (1.60±0.31) expression significantly reduced (P<0.05) . Conclusion GBS can reduce blood glucose in T2DM rats while improving glucose tolerance and hyperglycemia, and the mechanism appears to be associated with a decrease of hepatic PEPCK mRNA and protein expression.
作者 聂哲群 吴惧 徐键 尹敏 程楠 王馨悦 尹家俊 Nie Zhequn;Wu Ju;Xu Jian;Yin Min;Cheng Nan;Wang Xinyue;Yin Jiajun(Department qf Hepatobiliary Laparoscopic Surgery, Affiliated Zhongs han Hospital of Dalian University, Dalian 116001, China)
出处 《中华内分泌外科杂志》 CAS 2018年第6期446-449,共4页 Chinese Journal of Endocrine Surgery
基金 辽宁省自然科学基金资助项目(201102006) 辽宁省教育厅基金资助项目(2009A073).
关键词 胃旁路手术 2型糖尿病 磷酸烯醇丙酮酸羧激酶 糖异生 Gastric bypass surgery Type 2 diabetes mellitus Phosphoenolpyruvatecarboxykinase Gluconeogenesis
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