·糖尿病基础研究·

　　张远远、刘 星、何 君、姜晓亮、杨志伟

　　作者单位：100021北京，中国医学科学院北京协和医学院医学实验动物研究所, 卫生部人类疾病比较医学重点实验室

　　AMPK基因在C57BL/6J小鼠糖脂代谢中的作用

　　【摘要】 目的  研究腺苷酸活化蛋白激酶(AMPK)基因在C57BL/6J小鼠糖脂代谢中的作用。 方法  分别取5周龄AMPK基因敲除(AMPK-KO)小鼠和C57BL/6J对照小鼠各24只，分为正常饲料(ND)喂养和高脂高糖饲料(HFD)喂养两组。喂养12周，每两周测定小鼠禁食4 h血糖(FBG)，实验结束前行口服糖耐量实验(OGTT)，解剖取样，检测血生化指标、脂酶活性及相关蛋白的表达。 结果  AMPK-KO小鼠血糖、TC、LDL-C、HbA1c、6-磷酸葡萄糖脱氢酶(G6PD)活性、糖原合成酶激酶(GSK)活性、肝脏PPARγ蛋白表达量明显高于对照小鼠(P<0.05);其胰岛素含量、肝糖原含量、肌糖原含量、肝脂酶(HL)活性、脂蛋白酯酶(LPL)活性、总脂酶活性、葡萄糖激酶(GK)活性、肝组织P-AMPK蛋白、葡萄糖转运蛋白4(GluT-4)蛋白的表达量低于对照组(P<0.05)。 结论  AMPK基因通过调节C57BL/6J小鼠糖脂代谢，在T2DM的发病中起重要作用。

　　【关键词】糖尿病;腺苷酸活化蛋白激酶;C57BL/6J小鼠

　　doi:10.3969/j.issn.1006-6187.2011.12.015

　　The role of AMPK gene in glucose and lipid metabolism in C57BL/6J miceZHANG Yuan-yuan, LIU Xing, HE Jun, et al. Institute of Laboratory Animal Science, Chinese Academy of Medical Science(CAMS), and Pecking Union Medical College(PUMC). Key Laboratory of Human Disease Comparative Medicine, Ministry of Health, Beijing 100021, China

　　【Abstract】Objective   To investigate the role of AMPK gene in regulating glucose and lipid metabolism.Methods   We used 24 C57BL/6J mice and 24 AMPK gene knock-out mice (AMPK-KO) at five weeks old, fed with normal diet (ND)and high-glucose-fat diet (HFD)separately for 12 weeks. The blood glucose and fasting blood glucose were measured every 2 weeks. The capability of glucose tolerance was measured before the experiment was terminated. The blood/serum biochemical indicators, the enzyme activities and glycogen content were observed after 12-week’s feeding. The expressions of P-AMPK, GluT-4 and PPARγ proteins in liver were detected.   Result   The blood glucose level, fasting blood glucose, the peak glucose of OGTT, the level of TC, LDL and HbA1c, the activity of G6PD and GSK in serum and the expression of PPARγ proteins were higher in liver in AMPK-KO mice than in C57BL/6J control mice (P<0.05). The level of hepatic and muscle’s glycogen, the activity of lipase and GK, the expression of P-AMPK and GluT-4 proteins were lower in AMPK-KO mice than in control C57BL/6J mice (P<0.05). Conclusion   The AMPK gene plays an important role in the pathogenesis of type 2 diabetes through regulating the glucose and lipid metabolism in C57BL/6J mice.

　　【Key words】Diabetes mellitus; AMPK gene; C57BL/6J mice