钒酸钠治疗增加实验性糖尿病大鼠骨骼肌GLUT4表达的研究

目的探讨钒酸钠类胰岛素作用及骨骼肌GLUT4(葡萄糖转运蛋白4)在其作用中机制.方法 Wistar大鼠40只,体质量180～250 g,随机分为2组,一组应用链脲佐菌素(55 mg/kg)腹腔内注射,5 d后血糖大于13.5 mmol/L定为糖尿病大鼠,另一组为正常对照鼠,然后将正常对照组与糖尿病组大鼠各随机分为2组.加钒组隔日管饲0.4%钒酸钠水稀释液,对照组饮用0.9%生理盐水,观察基本指标变化,持续2周后在麻醉情况下迅速分离提取骨骼肌及血液标本,应用Western blot 和RT-PCR技术测定GLUT4的蛋白和基因表达.结果钒酸钠治疗糖尿病大鼠PG、TG、INS降低,糖尿病大鼠GLUT4蛋白和GLUT4mRNA表达与正常对照组比较降低明显,钒酸钠治疗糖尿病大鼠GLUT4蛋白和GLUT4mRNA表达增加接近正常对照组水平.结论钒酸钠治疗糖尿病大鼠在不增加胰岛素释放的情况下具有明显改善糖脂代谢的效果,使降低GLUT4水平恢复接近正常,说明钒酸钠增加糖尿病大鼠骨骼肌GLUT4表达使周围组织葡萄糖摄取利用紊乱增加可能是降低血糖机制之一.

Vanadium increases GLUT4 expression in skeletal muscles of streptozotocin-induced diabetic rats

Objective To investigate the insulin mimetic effects and the mechanism of the effects of glucose transport protein 4 (GLUT4) expression in the skeletal muscles of the streptozotocin (STZ) induced diabetic rats after vanadium treatment. Methods Male Wistar rats (180 250 g) were divided randomly into two groups. Rats in the first group received intraperitoneal injection at a single dose of STZ (55mg/kg), but those in the second group received vehicle. At 5 d following STZ injection (plasma glucose >13.5 mmol/L), diabetic rats received treatment of 0.4% vanadium (DT), but rats in the other group remained untreated (D). Control rats received 0.4% vanadium treatment (CT), but those in the other group remained untreated (C). After four weeks of treatment, rats were sacrificed, and then skeletal muscles and blood samples were quickly isolated and collected. Expressions of GLUT4 protein and mRNA were determined by Western blot and RT PCR techniques. Results The expression levels of GLUT4 protein and GLUT4 mRNA were significantly lower than those in the normal control. After treatment with vanadium, levels of plasma glucose, triglyceride, and insulin in diabetic rats decreased, but GLUT4 protein and GLUT4 mRNA expressions increased, and were similar to those in the normal control group. Conclusion Vanadium can significantly ameliorate the metabolic disorder of glucose and lipid without increasing insulin secretion and markedly increase GLUT4 expression in the diabetic rats, suggesting that vanadium induced increase of GLUT4 gene expression in the skeletal muscles of diabetic rats may be one of the mechanisms in the improvement of glucose uptake and utilization in the peripheral tissues.