摘要
目的探讨舒林酸对高脂饲养肥胖大鼠胰岛素敏感性的影响以及对胰岛素靶组织受体后信号转导途径蛋白表达及其磷酸化的调节作用。方法3周龄雄性SD大鼠20只随机分组给予普通饲料(5只)、高脂饲料(15只)饲养20周,用口服葡萄糖糖耐量试验筛选胰岛素抵抗造模成功大鼠共10只,再随机分组,予高脂饲料或高脂饲料加舒林酸干预,4周后以高胰岛素正葡萄糖钳夹试验评价不同干预组大鼠胰岛素敏感性变化。Western blot观察胰岛素受体底物1(IRS1)丝氨酸(Ser)/酪氨酸(Tyr)残基磷酸化水平的状态。结果高胰岛素正糖钳夹实验表明高脂饲养组大鼠葡萄糖清除率显著下降,提示胰岛素抵抗大鼠模型成功建立。舒林酸干预组大鼠葡萄糖清除率较高脂饲养组大鼠显著上升。舒林酸干预组大鼠骨骼肌IRS1酪氨酸磷酸化表达上调,而丝氨酸磷酸化表达下降。结论舒林酸通过调节IRS1 Ser/Tyr残基的磷酸化水平,改善高脂饮食肥胖大鼠的胰岛素敏感性。
Objective To explore the influence of sulindac on insulin sensitivity in obese rats induced by high fat diet and investigate the effects of interfering in inflammation pathway on the insulin signal transduction expression of insulin receptor substrate1(IRS1)and its Ser/Tyr phosphorylation.Methods Twenty male SD rats,three weeks old,were divided into two groups:CHOW(n=5/group),HFD group(n=15/group).20 weeks after feeding,oral glucose tolerance test and insulin releasing test were performed for estimating insulin sensitivity.Continued to take high fat diet,10 rats of insulin resistance induced by high fat feed diet were subdivided into two groups randomly(n=5/group):high fat diet and high fat diet plus sulindac for periods of 4 weeks.The insulin sensitivity in different groups were estimated by hyperinsulinemic-euglycemic clamp technique.The expression of IRS1 protein and its Ser/Tyr phosphorylation in rat insulin target tissues were detected by western blot.Results Hyperinsulinemic–euglycemic clamp study revealed a significantly impaired insulin action after high-fat feeding as compared with the CHOW group,indicating onset of high-fat induced insulin resistance.Glucose disposal rate was significantly higher in sulindac treatment group than that of HFD control group.There was a significant decrease in expression of the IRS1 Ser phosphorylation in skeleton muscle of rats treated with sulindac,while the expression of IRS1 Tyr phosphorylation was increased.Conclusions Treatment with sulindac could in part improve insulin resistance of obese rats probably through regulating the expression of IRS1 Ser/Tyr phosphorylation.
作者
顾鸣宇
林毅
马宇航
熊川浩
盖显英
丁晓颖
彭永德
Gu Mingyu;Lin Yi;Ma Yuhang;Xiong Chuanhao;Gai Xianying;Ding Xiaoying;Peng Yongde(Department of Endocrinology and Metabolism,Shanghai General Hospital of Nanjing Medical University,Shanghai General Hospital of Nanjing Medical University,Shanghai 200080,China)
出处
《中国临床保健杂志》
CAS
2022年第4期511-514,共4页
Chinese Journal of Clinical Healthcare
基金
上海申康医院发展中心临床三年行动计划资助项目(SHDC2020CR1016B)
上海交通大学“交大之星”医工滚动支持项目(YG2019GD05)
上海交通大学医学院多中心临床研究项目(DLY201824)
上海市松江卫计委松江区第三周期人才学科建设和疾病联合攻关合作项目(0702N18003)
上海市第一人民医院临床研究创新团队项目(CTCCR-2018A02)
松江区新一轮医学重点学科建设计划项目资助(ZK2019B02)。