细胞因子信号转导抑制因子3对糖尿病大鼠胰岛素受体底物1及其丝氨酸磷酸化水平的影响

目的 观察糖尿病大鼠肝脏和骨骼肌中细胞因子信号转导抑制因子3(SOCS-3)、胰岛素受体底物1(IRS-1)及丝氨酸磷酸化胰岛素受体底物1(PIRS-1Ser307)水平，探讨其在胰岛素抵抗发生中的机制。 方法 将40只雄性SD大鼠按随机数字表法分为对照组(20只)和糖尿病组(20只)。对照组大鼠予以普通饲料喂养，糖尿病组大鼠予以高糖高脂饲料喂养4周后腹腔注射链脲霉素，其中16只大鼠制成2型糖尿病模型。采用实时荧光定量PCR法检测大鼠肝脏和骨骼肌中SOCS-3、IRS-1 mRNA水平，Western blot法检测大鼠肝脏和骨骼肌中SOCS-3、IRS-1、PIRS-1Ser307蛋白水平。应用t检验及Pearson直线相关进行数据分析。 结果 ①与对照组相比，糖尿病组大鼠肝脏和骨骼肌SOCS-3 mRNA显著升高(P＜0.05)，IRS-1 mRNA显著降低(P＜0.05)；糖尿病组大鼠肝脏和骨骼肌SOCS-3和PIRS-1Ser307蛋白显著升高(P＜0.05)，IRS-1蛋白显著降低(P＜0.05)；②糖尿病组大鼠肝脏和骨骼肌SOCS-3蛋白与IRS-1蛋白呈负相关(r=-0.865、-0.756，P＜0.05)，与PIRS-1Ser307蛋白呈正相关(r=0.678、0.663，P＜0.05)。 结论 糖尿病大鼠可能通过上调SOCS-3基因，增加IRS-1丝氨酸磷酸化水平和降低IRS-1表达，诱发胰岛素抵抗。 

Effect of suppressor of cytokine signaling 3 on insulin receptor substrate-1 and its serine phosphorylation in diabetes rat models

Objective To observe the expression of suppressors of cytokine signaling 3(SOCS-3),insulin receptor substrate-1(IRS-1)and phospho-IRS-1(PIRS-1Ser307)in liver and skeletal muscle,and to explore molecular mechanisms of insulin resistance in diabetes rats models. Methods Forty male SD rats were randomly divided into two groups,the control group(20 male rats)fed with standard diet,and the Diabetes group(20 male rats)were fed with high sucrose-fat diet for 4 weeks and then injected intraperitoneally with streptozotocin(STZ),16 male rats met the criteria of type-2 diabetes.The expressions of SOCS-3,IRS-1 and PIRS-1Ser307 in liver and skeletal muscle were detected by Real-time PCR and Western blot.The data were analyzed by T-test and Pearson linear correlation analysis. Results ①AS compared with control group,diabetes group showed that mRNA and protein expression of IRS-1 of liver and skeletal muscle were decreased(P<0.05),the expression of SOCS-3 and PIRS-1Ser307 were increased(P<0.05).②The expression of SOCS-3 in liver and skeletal muscle were negatively correlated with IRS-1(r=-0.865,-0.756,P<0.05) and positively with PIRS-1Ser307 in diabetes group(r=0.678,0.663,P<0.05). Conclusion Diabetes rats possibly produced insulin resistance by up-regulating SOCS-3 expression,by decreasing IRS-1 and increasing its serine phosphorylation levels in liver and skeletal muscle.