Acute effects of exogenous nitric oxide on glucose uptake in skeletal muscle of normoglycaemic and diabetic rats

Background: The role of nitric oxide (NO) in the modulation of basal and insulin-stimulated glucose uptake remains controversial. The aim of this study was to investigate the role of NO released from its donors, S-nitrosoglutathione (GSNO) and S-nitroso-N-acerylpenicillamine (SNAP), on glucose uptake in skeletal muscle of normoglyceamic and type 2 diabetic rats. Material/Methods: Skeletal muscle strips of type 2 diabetic and normoglycaemic Sprague-Dawley rats were incubated with or without various concentrations (200 mu M, 500 mu M, 1000 mu M, 10 mM & 20 mM) of SNAP or GSNO in the presence or absence of insulin (100 nM or 10 mu M). The associated radioactivity was determined by liquid scintillation counting in a Beckman LS6000 scintillation counter programmed for dual-channel counting. Results: SNAP and GSNO at 1000 mu M significantly elevated basal and insulin-stimulated 2-deoxyglucose uptake (P < 0.05) in normoglycaernic and diabetic rats. Millimolar concentrations (10 & 20 mM) of GSNO and SNAP significantly decreased basal and insulin-stimulated glucose uptake in skeletal muscle strips of normoglycaemic and type 2 diabetic rats in a concentration-dependent manner (P < 0.05). The inhibition of insulin-stimulated glucose uptake was greater in the diabetic rats using both NO donors compared with normoglycaemic rats (P < 0.05). Conclusions: The stimulatory effect of micromolar concentrations of GSNO and SNAP enhances basal and insulin-stimulated glucose uptake in normoglycaemic and type 2 diabetic rats, however higher concentrations elicited an inhibitory effect in nonnoglycaemic and diabetic rats. This highlights the NO-glucose uptake mechanism as a possible potential therapeutic target in the treatment of type 2 diabetes.