Effects of the nitric oxide donor, sodium nitroprusside, on resting leg glucose uptake in patients with type 2 diabetes

Aims/hypothesis: Nitric oxide (NO) has been implicated as an important signalling molecule in the contraction-mediated glucose uptake pathway and may represent a novel strategy for blood glucose control. The current study sought to determine whether acute infusion of the NO donor, sodium nitroprusside (SNP), increases leg glucose uptake at rest in patients with type 2 diabetes.

Methods: Fifteen male patients with type 2 diabetes (aged 54 ± 4 years, mean ± SD) were entered into a randomised, cross-over design study, examining the effect of a 30-min intra-femoral infusion of SNP on leg glucose uptake. Comparison was made with a 30-min infusion of verapamil, titrated to elicit similar leg blood flow responses to SNP. Leg blood flow was measured by thermodilution in the femoral vein, and leg glucose uptake was calculated as the product of leg blood flow and the femoral arterio-venous (A-V) glucose concentration gradient.

Results: The two drugs increased leg blood flow to a similar extent (p = 0.50). Both leg A-V glucose concentration gradient (SNP 0.12 ± 0.05, verapamil -0.06 ± 0.04 mmol/l; mean± SEM, p = 0.03) and leg glucose uptake (SNP 0.17 ± 0.09, verapamil -0.09 ± 0.06 mmol/min; p = 0.03) were higher with the SNP treatment than with verapamil. These results occurred independently of any significant difference in plasma insulin concentration between drugs (p = 0.56).

Conclusions/interpretation: Acute infusion of SNP resulted in greater glucose uptake relative to verapamil. NO may therefore be an important mediator of peripheral glucose disposal and a potential therapeutic target in patients with type 2 diabetes.