Effect of insulin on protein phosphatase 2A expression in muscle in type 2 diabetes

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.