Yang Yang, Xiao Meifang, Mao Yiqing, Li Hui, Zhao Shuyong, Gu Yi, Wang Rong, Yu Jianqiang, Zhang Xuemei, Irwin David M, Niu Gang, Tan Huanran
Department of Pharmacology, Peking University, Health Science Center, Beijing 100191, China.
Biomed Pharmacother. 2009 Jun;63(5):366-74. doi: 10.1016/j.biopha.2008.06.033. Epub 2008 Jul 9.
Resistin has been considered to link obesity with type 2 diabetes. Liver glycogen metabolism plays an essential role in maintaining glucose homeostasis, we investigated the effect of resistin on liver glycogen metabolism and attempted to identify its role in initiating insulin resistance and type 2 diabetes. Primary culture of rat hepatocytes was treated by resistin and insulin. Glycogen content was determined by the anthrone-reagent method. Real-time PCR, Western blot and enzymatic activity assay were used to detect key enzymes and genes involved in glucose metabolism. Hepatocytes exposed to resistin, but only in the presence of insulin, show a decrease in insulin-stimulated glycogen content. Decreased insulin receptor expression and GS activity and elevated GP activity was observed after the treatment of hepatocytes with resistin. No significant changes in the expression of the genes for these proteins were observed. These results strongly suggest that resistin effects glycogen metabolism at the protein level, and resistin is highly associated with insulin resistance and type 2 diabetes and is a candidate for the prevention and treatment of type 2 diabetes. Our results should lead to the development of novel strategies for the treatment of type 2 diabetes.
抵抗素被认为是将肥胖与2型糖尿病联系起来的因素。肝糖原代谢在维持葡萄糖稳态中起着至关重要的作用，我们研究了抵抗素对肝糖原代谢的影响，并试图确定其在引发胰岛素抵抗和2型糖尿病中的作用。用抵抗素和胰岛素处理大鼠原代肝细胞培养物。用蒽酮试剂法测定糖原含量。采用实时PCR、蛋白质印迹法和酶活性测定法检测参与葡萄糖代谢的关键酶和基因。仅在胰岛素存在的情况下，暴露于抵抗素的肝细胞显示胰岛素刺激的糖原含量降低。用抵抗素处理肝细胞后，观察到胰岛素受体表达和糖原合成酶（GS）活性降低，糖原磷酸化酶（GP）活性升高。这些蛋白质的基因表达未观察到显著变化。这些结果强烈表明，抵抗素在蛋白质水平上影响糖原代谢，并且抵抗素与胰岛素抵抗和2型糖尿病高度相关，是2型糖尿病预防和治疗的一个候选因素。我们的结果应该会推动2型糖尿病治疗新策略的发展。
