咖啡对胰岛素抵抗大鼠胰岛素受体底物及其酪氨酸、丝氨酸磷酸化的影响  

Effects of coffee on insulin receptor substance and its tyrosine /serine phosphorylation in rats with insulin resistance

作　　者：陈琳[1] 喻明[1] 夏娟[1] 高月锦[1] 

机构地区：[1]上海市普陀区中心医院,上海200062

出　　处：《山东医药》2014年第20期20-23,27,共5页Shandong Medical Journal

基　　金：上海市教育委员会预算内项目(2010JW63)

摘　　要：目的观察咖啡对胰岛素抵抗大鼠脂肪组织胰岛素受体底物(IRS)-1、IRS-2及其酪氨酸、丝氨酸磷酸化的影响,评估咖啡对脂肪组织胰岛素受体后信号转导途径影响。方法 Wistar大鼠40只随机分为正常NC、CC、DC、IR组,每组10只。NC组予正常饮食,CC组、DC组及IR组给予高脂饮食,CC组及DC组每日分别以含咖啡因咖啡和去咖啡因咖啡灌胃。12周后行口服葡萄糖耐量试验(OGTT);根据空腹血清胰岛素和空腹血糖水平及HOMA-胰岛素抵抗指数(HOMA-IR)反映外周组织胰岛素敏感性;RT-PCR检测大鼠脂肪组织IRS-1、IRS-2 mRNA及蛋白表达;Western blot测定脂肪组织IRS-1酪氨酸磷酸化和丝氨酸磷酸化程度。结果 OGTT显示IR组60和120min血糖高于NC组(P分别<0.05、0.01)。IR组、CC组及DC组空腹血清胰岛素水平均高于NC组(P均<0.05)。IR组HOMA-IR高于NC组、CC组和DC组(P均<0.05)。NC组、CC组脂肪组织IRS-1 mRNA相对表达量均高于IR组(P均<0.01),IRS-2 mRNA表达各组无显著差异(P均>0.05)。各组大鼠脂肪组织IRS-1、IRS-2蛋白含量无明显差异(P均>0.05)。NC组、CC组、DC组脂肪组织IRS-1酪氨酸磷酸化水平高于IR组(P均<0.05),丝氨酸磷酸化水平低于IR组(P均<0.05)。结论咖啡灌胃可改善高脂饮食大鼠胰岛素抵抗,其机制可能通过改变脂肪组织IRS-1转录及其酪氨酸/丝氨酸磷酸化水平,影响胰岛素抵抗大鼠胰岛素受体后信号转导。Objective To observe the effect of coffee on the expression of insulin receptor substance （ IRS）-1 and IRS-2 and their tyrosine/serine phosphorylation in rats with insulin resistance （ IR） and to evaluate its effect on the post-re-ceptor signal transduction in adipose tissues .Methods Totally 40 Wistar rats were randomly divided into the normal con-trol （ NC） group, caffeinated coffee lavage （ CC） group, decaffeinated coffee lavage （ DC） group, and IR （ IR） group, with 10 rats in each group .Except for NC group , the other three groups were given high fat diet .Meanwhile , CC and DC groups, respectively, were treated with caffeinated coffee and decaffeinated coffee daily lavage for 12 weeks.Then the oral glucose tolerance test （OGTT） was given and homeostasis model assessment of insulin resistance （HOMA-IR） was em-ployed to assess the degree of insulin resistance .The levels of IRS-1 and IRS-2 and their mRNA in adipose tissues were de-tected by RT-PCR.And the tyrosine/serine phosphorylation was measured by Western blotting .Results IR group had higher blood glucose levels at the time of 60 and 120 min as compared with NC group （P〈0.05, P〈0.01, respectively）. CC, DC, and IR groups displayed higher fasting insulin levels than NC group （all P〈0.05）.However, HOMA-IRs of CC, DC, and NC groups were all significantly lower than that of IR group （all P〈0.05）.Although no significant differ-ences were found in the levels of IRS-1 and IRS-2 as well as IRS-2 mRNA among the four groups （P〉0.05）, IRS-1 mR-NA of the NC and CC groups was higher than that of the IR group （all P〈0.01）.Higher tyrosine phosphorylation and low-er serine phosphorylation were exhibited in NC , CC, and DC groups as compared with the IR group （all P〈0.05）.Con-clusions Insulin resistance induced by high fat diet could be alleviated by coffee , whose mechanism may be explained by its effect on post-receptor signal transduction in adipose tissues by the alteration of IRS-1 mRNA as well as

关 键 词：胰岛素抵抗 咖啡 胰岛素受体底物 酪氨酸 丝氨酸 

分 类 号：R587[医药卫生—内分泌]