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  • Title: Effect of early insulin therapy on nuclear factor kappaB and cytokine gene expressions in the liver and skeletal muscle of high-fat diet, streptozotocin-treated diabetic rats.
    Author: Bi Y, Sun WP, Chen X, Li M, Liang H, Cai MY, Zhu YH, He XY, Xu F, Weng JP.
    Journal: Acta Diabetol; 2008 Sep; 45(3):167-78. PubMed ID: 18500427.
    Abstract:
    To clarify the effect of early insulin therapy on nuclear factor kappaB (NFkappaB) 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 kappaB (IkappaBalpha) protein and a decrease in NFkappaB p65 DNA binding activity. A decreased level in mRNAs encoding tumor necrosis factor (TNF)alpha in the liver and muscle and interleukin (IL)-1beta in the liver were observed. Our results suggested that early insulin treatment inhibits NFkappaB 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.
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