不同糖尿病模型小鼠糖原代谢变化的研究

Comparative study on changes of glycogen metabolism in model mice of diabetes mellitus

目的:通过观察不同类型糖尿病动物模型糖原代谢的变化,初步探讨糖原代谢异常在糖尿病发病过程中的作用。方法:首先建立4种糖尿病小鼠模型:四氧嘧啶诱导模型、STZ诱导模型、n5STZ诱导模型和葡萄糖激酶基因敲除模型,并对模型小鼠血糖水平进行检测。然后测定上述动物模型肝糖原和肌糖原的含量,并采用Westernblot方法对葡萄糖激酶基因敲除模型鼠肝组织中葡萄糖激酶的蛋白表达量进行测定。结果:血糖检测结果显示各模型组空腹血糖值均显著高于对照组,表明糖尿病造模基本成功。除n5STZ诱导模型外,其它模型组肝糖原的含量均明显低于对照组。此外,与对照组比较,4种糖尿病模型肌糖原含量均显著降低。Westernblot结果表明葡萄糖激酶基因敲除模型鼠肝组织中葡萄糖激酶的蛋白表达显著降低,这可能是该模型肝糖原含量减少的机制之一。结论:糖尿病动物模型出现糖原代谢异常,表现为肝糖原和肌糖原减少,提示糖原代谢在糖尿病发病过程中起着重要的作用。

AIM: To explore the changes of glycogen metabolism in diabetic animal models and the role of glycogen metabolism in the pathogenesis of diabetes mellitus. METHODS: Firstly four types of diabetic animal models were generated including mice models of type 1 and type 2 diabetes mellitus. Then the liver glycogen and muscle glycogen contents of these diabetic mice were determined according to anthrone-reagent method and glucokinase expressions in liver of glucokinase gene knockout mice were assayed using western blot. RESULTS: Blood glucose levels were increased in all types of model mice. In particularly, model mice of type 1 diabetes mellitus displayed significantly higher blood glucose levels than those of model mice of type 2 diabetes mellitus. Liver glycogen contents in model mice significantly declined except neonatal STZ-induced model mice. In addition, muscle glycogen contents were decreased in all model mice. Western blot assay showed that glucokinase expression decreased in liver from glucokinase gene knockout mice, which might contribute to the diminished liver glycogen in this kind of diabetes model. CONCLUSION: Diabetic subjects show impaired glycogen metabolism with the diminished liver glycogen and muscle glycogen contents, which indicates the key role of glycogen metabolism in the pathogenesis of diabetes.