不同方式急性运动结合二甲双胍改善2型糖尿病小鼠血糖稳态及肝脏糖异生的作用  

Different Acute Exercise Combined with Metformin Improving Glucose Homeostasis and Hepatic Gluconeogenesis in Type 2 Diabetic Mice

作　　者：沈文清 张强[1,2] 张怡[1,2] 漆正堂[1,2] 孙易 丁树哲[1,2] SHEN Wenqing;ZHANG Qiang;ZHANG Yi;QI Zhengtang;SUN Yi;DING Shuzhe(Key Laboratory of Adolescent Health Assessment and Exercise Intervention,Ministry of Education,East China Normal University,Shanghai 200241,China;School of Physical Education and Health,East China Normal University,Shanghai 200241,China)

机构地区：[1]华东师范大学青少年健康评价与运动干预教育部重点实验室,上海200241 [2]华东师范大学体育与健康学院,上海200241

出　　处：《首都体育学院学报》2019年第6期560-569,共10页Journal of Capital University of Physical Education and Sports

基　　金：国家自然科学基金资助项目(31671241)

摘　　要：探讨不同方式急性运动结合二甲双胍对2型糖尿病小鼠血糖稳态及肝脏糖异生的作用,从运动中血糖变化、肝脏糖异生及调控因子相关mRNA表达水平的角度为治疗2型糖尿病提供新的运动处方和研究靶点。方法:采用4周高脂膳食结合链脲佐菌素(STZ,100 mg/kg)方法构建2型糖尿病小鼠模型,建模成功后随机分为NC、NCR、NCE、DC、DCR、DCE、HMC、HMR和HME共9组,每组8只小鼠。HMC、HMR和HME小鼠在末次运动前腹腔注射200 mg/kg HCloMetformin溶液,NC和DC组小鼠相应腹腔注射0.9%生理盐水。NCR、DCR和HMR小鼠进行急性抗阻运动;NCE、DCE和HME小鼠进行急性耐力运动。末次运动结束后3 h处死小鼠并取样。采用ELISA及RT-PCR技术检测相关血清指标和相关基因mRNA表达。结果:4周高脂膳食结合一次性腹腔注射STZ(100 mg/kg)成功构建2型糖尿病小鼠模型;相比DCE和DCR小鼠,HME和HMR小鼠血糖值和血糖波动幅度都显著下降;相比于HMC小鼠,HMR和HME小鼠附睾白色脂肪组织重量百分比、血清葡萄糖、血清TG和肝脏乳酸/丙酮酸浓度比值都显著下降,HMR组小鼠GSP和血清T-CHO显著降低,而HMR和HME小鼠肝糖原含量显著升高;相比HMC小鼠,HMR和HME小鼠肝脏糖异生相关因子PEPCK、G6pc和Gck mRNA表达显著升高,肝脏FBP和GLUT2 mRNA表达显著降低;相比于HMC小鼠,HMR和HME小鼠调控肝脏糖异生相关因子AMPKα2、CREB、PGC-1α、Keap1和Nrf2 mRNA表达都显著升高,且HMR小鼠肝脏AMPKα1 mRNA表达显著升高。结论:急性抗阻运动和急性耐力运动结合二甲双胍均可改善2型糖尿病小鼠运动中血糖的稳态,但急性抗阻运动结合二甲双胍能更有效改善2型糖尿病小鼠血糖稳态和肝脏糖异生情况。其中机制可能为不同方式的急性运动结合200 mg/kg剂量的二甲双胍可显著增加2型糖尿病小鼠肝脏AMPK-CREB-PGC-1α-PEPCK/G6Pase/GLUT2信号通路mRNA的表达。Objective:The purpose of the present study was to investigate the effects of different acute exercise combined with metformin on glucose homeostasis and hepatic gluconeogenesis in type 2 diabetic mice,hoping to provide new exercise treatment prescriptions and study protein targets for curing type 2 diabetes from the perspective of the glucose homeostasis in acute exercise,hepatic gluconeogenesis and regulatory factors relative mRNA level expression.Methods:The type 2 diabetic mice were established by feeding high fat diet and intraperitoneal injection with STZ(Streptozotocin,100mg/kg).These mice were divided into 9 groups randomly,such as Normal Control group(NC),Normal Control Resistance Exercise group(NCR),Normal Control Endurance Exercise group(NCE),Diabetic Control group(DC),Diabetic Control Resistance Exercise(DCR),Diabetic Control Endurance Exercise(DCE),High dose of Metformin Control group(HMC),High dose of Metformin acute Resistance Exercise group(HMR)and High dose of Metformin acute Endurance Exercise group(HME),n=8 in each group.HMC,HMR and HME group mice were intraperitoneally injected with HCl·Metformin solution(200mg/kg weight)and NC and DC group mice were intraperitoneally injected with 0.9%saline.NCR,DCR and HMR group mice performed acute resistance exercise;NCE,DCE and HME group mice performed acute endurance exercise.All mice were sacrificed and selected with samples in 3 hours after acute exercise.ELISA was used for examining relative serum indicators and RT-PCR was used for testing relative gene mRNA expression.Results:The protocol of 4-week high fat diet and one time intraperitoneal injection with STZ successfully developed the model of type 2 diabetic mice.Compared to DCE and DCR group mice,blood glucose and the fluctuation change were significantly decreased in HME and HMR group mice.Compared to HMC group mice,the percentage of epididymal white adipose tissue content,serum glucose,serum TG and hepatic[lactate]/[pyruvate]ratio were all significantly decreased in HMR and HME group mice,glycos

关 键 词：急性抗阻运动 急性耐力运动 二甲双胍 血糖稳态 肝脏糖异生 

分 类 号：G[文化科学]