Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes
Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes
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DOI：
10.1046/j.1365-2362.2002.01098.x
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发表时间：
2002-12-01
影响因子：
5.5
通讯作者：
Beck-Nielsen, H
中科院分区：
文献类型：
--
作者：
Hojlund, K;Poulsen, M;Beck-Nielsen, H
背景蛋白磷酸酶2A（PP 2A）作用于参与胰岛素调节葡萄糖摄取和糖原合成的许多酶。本研究旨在探讨胰岛素对2型糖尿病和对照组骨骼肌PP 2A表达的影响。材料与方法采用正血-高胰岛素钳夹技术结合间接量热法对10例2型糖尿病和10例对照组进行研究。结果2型糖尿病患者胰岛素介导的葡萄糖处理、葡萄糖氧化和非氧化性葡萄糖代谢均减少，而脂质氧化增加（P均< 0.05）。胰岛素下调对照组骨骼肌PP 2A-C α的表达（P < 0.05），但对2型糖尿病患者无明显影响。在对照组中，胰岛素介导的PP 2A-Calpha减少与胰岛素介导的葡萄糖处理、葡萄糖氧化、非氧化性葡萄糖代谢增加（均P< 0.05）和脂质氧化减少（P < 0.01）相关。在2型糖尿病受试者中，这些关系是absent.Conclusions下调PP 2A-Calpha表达的胰岛素在骨骼肌中似乎与正常的胰岛素作用葡萄糖储存，葡萄糖和脂质氧化。胰岛素对PP 2A-Calpha表达的下调受损可能是胰岛素抵抗的标志物，并有助于2型糖尿病的发病机制。
Background Protein phosphatase 2A (PP2A) acts on a number of enzymes involved in the insulin regulation of glucose uptake and glycogen synthesis. This study was carried out to investigate the effect of insulin on PP2A expression in skeletal muscles of type 2 diabetic and control subjects.Material and methods Ten type 2 diabetic and 10 matched, control subjects were studied using the euglycaemic-hyperinsulinaemic clamp technique combined with indirect calorimetry. Immunoreactive protein levels of the catalytic a subunit of PP2A (PP2A-Calpha) were measured in biopsies from the vastus lateralis muscle obtained in the basal and insulin-stimulated state.Results In type 2 diabetic subjects insulin-mediated glucose disposal, glucose oxidation and nonoxidative glucose metabolism were reduced, whereas lipid oxidation was increased (all P < 0.05). Insulin down-regulated PP2A-Cα expression in skeletal muscle of the control subjects (P < 0.05) but not in the type 2 diabetic subjects. In the control subjects, the insulin-mediated decrease in PP2A-Calpha correlated with the insulin-mediated increase in glucose disposal, glucose oxidation, nonoxidative glucose metabolism (all P< 0.05) and decrease in lipid oxidation (P < 0.01). In the type 2 diabetic subjects these relationships were absent.Conclusions Down-regulation of PP2A-Calpha expression by insulin in skeletal muscle seems to be associated with a normal insulin action on glucose storage, glucose and lipid oxidation. Impaired down-regulation of PP2A-Calpha expression by insulin may be a marker for insulin resistance and contribute to the pathogenesis of type 2 diabetes.