罗格列酮对胰岛素抵抗大鼠骨骼肌蛋白激酶B表达的影响

目的 :探讨胰岛素增敏剂罗格列酮对胰岛素抵抗大鼠骨骼肌蛋白激酶B(PKB)表达的影响。方法 :应用高脂饲料喂养复制胰岛素抵抗大鼠模型。应用Westernblotting方法检测骨骼肌中PKB的表达。结果 :持续高脂饲料喂养组大鼠产生了明显胰岛素抵抗 ,骨骼肌PKB的表达较正常对照组显著降低 (OD值 8.2 4±s 0 .11vs 9.36± 0 .18,P <0 .0 1) ,罗格列酮治疗组和正常饲料替代组大鼠胰岛素抵抗明显改善 ,PKB的表达较持续高脂饲料喂养组大鼠明显增加 (OD值分别为 8.89± 0 .0 8,8.4 0± 0 .0 9vs 8.2 4± 0 .11,P <0 .0 1)。结论 :高脂喂养的大鼠胰岛素抵抗的产生与骨骼肌胰岛素刺激的PKB表达降低有明显关系 ,罗格列酮能显著增加已经降低了的胰岛素抵抗大鼠骨骼肌中PKB的表达 ,部分恢复受损的胰岛素信号转导 ,进而明显改善胰岛素抵抗 ,这可能也是罗格列酮减轻胰岛素抵抗的作用机制之一。

Effect of rosiglitazone on protein kinase B expression of insulin resistant rats skeletal muscle

AIM: To study the effect of insulin sensitivity agonist—rosiglitazone on protein kinase B (PKB) expression of insulin resistant rats skeletal muscle. METHODS: Insulin resistant rat model was induced by high fat diet feeding. Thirty-nine male SD rats were randomly divided into two groups feeding either normal chow (NC, n=9) or high-fat diet(HF, n=30). After 2 mo, rats in group HF were randomly divided into three groups, high fat diet group (HFF, n=9), normal chow intervention group (HFN, n=9) and rosiglitazone intervention group (HFR, n=12). After 1 mo intervention treatment, all rats were fasted for 12 h. The rats were killed and skeletal muscles were isolated rapidly ten minutes after insulin (10 U·kg -1 body weigh) intraperitoneal injection. The PKB expressions were tested with Western blotting. RESULTS: The rats in group HFF developed obvious insulin resistance, their PKB expression of skeletal muscle (OD value 8.24±s 0.11 vs 9.36±0.18, P<0.01) decreased significantly compared with normal control group. Rats treated with rosiglitazone in group HFR and normal chow intervention in group HFN improved insulin resiatance obviously. Compared with group HFF, their PKB expression (OD value 8.89±0.08, 8.40±0.09 vs 8.24±0.11, P<0.01) increased significantly. CONCLUSION: Development of insulin resistance of rats which fed with high fat diet is obviously associated with suppression of insulin-stimulated PKB expression of skeletal muscle. Rosiglitazone can increase PKB expression of skeleted muscle and partially restore the impaired insulin signal transduction, and further improve insulin resistance. This may be one of the mechanisms which decreases the insulin resistance.