Abstract

Background: Insulin resistance is the central defect in obesity and type 2 diabetes. In Lipid accumulation and increased Protein Tyrosine Phosphatase-1B (PTP-1B) gene expression have been reported in muscle insulin resistance. The aim of this study was to investigate the effect of PTP-1B knockdown on glucose uptake and triglyceride levels in C2C12 cells. Methods: Reducing the expression of PTP-1B in C2C12 myoblasts was performed using the plasmids containing the shRNA against PTP-1B gene. PTP-1B protein level was assessed by western blot. The rate of glucose uptake and the intracellular triglyceride levels were evaluated in the PTP-1B knockdown and normal cells. Results: PTP-1B protein level in PTP-1B knockdown C2C12 cells decreased by 58 compared to the normal cells. Insulin-stimulated glucose uptake was decreased by palmitate in both the control and knockdown cells, whereas PTP1B knockdown cells treated with 0.5 and 0.75mM palmitate remained sensitive to the insulin with about 2.5 and 3-fold, respectively as well as increase in glucose uptake compared to the control cells. Treatment of the cells with 0.5 and 0.75mM palmitate resulted in 1.25 and 1.42 fold increase in triglyceride levels, respectively in the knockdown cells compared to the control cells. Conclusion: The results of this study suggest that increased insulin sensitivity in PTP-1B knockdown cells can be partly attributed to increased triglyceride levels within the muscle cells. Thus, reduced PTP-1B gene expression can be a potential therapeutic target for treating insulin resistance, type 2diabetes and metabolic syndrome.