Abstract
The purpose of this study was to investigate whether nitric oxide (NO) replacement or nitric oxide synthase (NOS) inhibition influences in vivo insulin action. The NO donor sodium nitroprusside (SNP, 3ng/kg/min), the NOS inhibitor NG-monomethyl-L-arginine (LNMMA, 1mg/kg/min), or saline was infused constantly during the euglycemic clamp procedure in healthy and STZ-induced diabetic rats. Insulin was infused at a rate of 3.0mU/kg/min in the awake condition. Plasma insulin levels during the insulin infusion were 30μU/ml, and the blood glucose level of the diabetic and healthy rats was clamped at 140mg/dl and fasting levels, respectively, by periodic adjustment of the i. v. glucose infusion rate. LNMMA administration significantly decreased the insulin-mediated glucose disposal rate (GDR) in diabetic rats (11.2±0.8 vs.7.0±0.7mg/kg/min, p<0.05). SNP administration, however, resulted in a significant increase in GDR (21.6±2.0mg/kg/min, p<0.01) in diabetic rats, and the metabolic clearance rate for glucose (MCR) in diabetic rats infused with SNP reached 87% of the level in the healthy rats. Neither SNP nor LNMMA administration affected GDR or MCR in healthy rats. It can be concluded that NO replacement improves in vivo insulin action in diabetic rats.
