Effect of early insulin therapy on nuclear factor κB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats

To clarify the effect of early insulin therapy on nuclear factor kappa B (NF kappa B) pathway and inflammatory cytokine responses in the liver and skeletal muscle in type 2 diabetes. High-fat diet and low dose streptozotocin (STZ) induced diabetic rats were given NPH insulin or gliclazide for 3 weeks initiated at the 3rd day after STZ injection as early treatment and NPH for 3 weeks at 1 month as late treatment. Intraperitoneal glucose tolerance test (IPGTT) was performed at 3rd day after the end of treatment. Early interventions caused a decrease in glucose-insulin index in IPGTT, promoted glucose transporter 4 (Glut4) gene and protein expressions in muscle and reduced phosphoenolpyruvate carboxykinase (PEPCK) protein levels in the liver. There was an increase in inhibitor kappa B (I kappa B alpha) protein and a decrease in NF kappa B p65 DNA binding activity. A decreased level in mRNAs encoding tumor necrosis factor (TNF)alpha in the liver and muscle and interleukin (IL)-1 beta in the liver were observed. Our results suggested that early insulin treatment inhibits NF kappa B activity and inflammatory cytokine responses in the liver and skeletal muscle that were involved in the amelioration of insulin resistance in type 2 diabetic rats.