中国仓鼠自发性2型糖尿病基础代谢特征及相关基因的表达差异

Characteristics of basal metabolism and expression of related genes in spontaneous type 2 diabetic Chinese hamster

目的 探究自发性2型糖尿病中国仓鼠糖脂代谢、体成分、昼夜运动及新陈代谢等基础代谢特征和相关基因在骨骼肌、肝中的表达情况。方法 根据中国仓鼠空腹血糖(FBG)和餐后血糖(PBG)值,选取对照组(FBG≤4.5 mmol/L且PBG<6.0 mmol/L)与糖尿病组(FBG≥6.0 mmol/L且PBG>7.0 mmol/L),测定动物体重、血糖、血脂、血清胰岛素含量及糖耐量,分析动物体成分,昼夜运动及新陈代谢特征,检测相关基因葡萄糖转运蛋白4(glucose transporter 4,Glut4)和过氧化物酶体增殖激活受体-γ(peroxisomeproliferative activated receptor-γ,Pparg)在骨骼肌和肝中的表达情况。结果 与对照组相比,中国仓鼠糖尿病组血糖、血脂含量增加,血清胰岛素含量和胰岛素抵抗指数(homeostasis model assessment of insulin resistance,HOMA-IR)增大,体脂率降低,摄食量和白天活动量增加,热量消耗增大。PPARG在肝和骨骼肌中的mRNA和蛋白表达水平显著增加;GLUT4在骨骼肌中的mRNA和蛋白表达水平显著降低。结论 自发性2型糖尿病中国仓鼠属于糖脂代谢异常,能产生胰岛素抵抗的非肥胖型2型糖尿病动物模型,GLUT4的下调可能与骨骼肌中异常的糖代谢及胰岛素抵抗有关,而上调的PPARG可能有利于机体胰岛素抵抗状态的缓解。

Objective To explore the basic metabolic characteristics and expression of related genes in the skeletal muscle and liver of Chinese hamsters with spontaneous type 2 diabetes,including glucose and lipid metabolism,body composition,diurnal movement,metabolism,and the expression of relevant genes.Methods We regarded the Chinese hamster with fasting blood glucose(FBG)higher than 6.0 mmol/L and post-prandial blood glucose(PBG)higher than 7.0 mmol/L as diabetic based on the mean and 95%frequency distribution values of FBG and PBG.12 hamsters at the age of 48 weeks in diabetic and control groups,each group was half male and female.Animal weight,blood glucose,blood lipid,serum insulin content,and glucose tolerance were measured.Animal body composition,diurnal movement,and metabolic characteristics were analyzed by InAlyzer Dual Energy X-ray Animal Body Composition Analysis System,High-throughput Behavior Analysis System,and Open Circuit Calorimetric Metabolic System,respectively.The expression of diabetes-related genes Glut4 and Pparg in skeletal muscle and liver were measured by Real-time PCR and Western blotting.Results In the diabetic group,blood glucose and lipid,serum insulin,food intake,daytime activity,and heat consumption were significantly increased,while the percentage of body fat was significantly decreased.Compared with the control group,the mRNA and protein expressions of PPARG in the liver and skeletal muscle were significantly increased,and the mRNA and protein expressions of GLUT4 in skeletal muscle were significantly decreased in diabetic hamsters.Conclusions This type 2 diabetic Chinese hamster model exhibits non-obese,abnormal glucose and lipid metabolism,and insulin resistance.The down-regulation of GLUT4 may be related to abnormal glucose metabolism and insulin resistance in skeletal muscle,while the up-regulated PPARG may alleviate insulin resistance in the liver.