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Systemic nitric oxide synthase inhibition increases insulin sensitivity in man
R Butler1, A D Morris, A D Struthers
1University Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, U.K.
Clinical Science (London, England : 1979)
|April 16, 1998
Summary
Systemic nitric oxide synthase inhibition with NG-monomethyl L-arginine unexpectedly increased whole-body glucose uptake and skeletal muscle blood flow in healthy males. This challenges the hypothesis that nitric oxide inhibition decreases insulin sensitivity.
Area of Science:
- Physiology
- Metabolism
- Cardiovascular Science
Background:
- Skeletal muscle blood flow is a key determinant of insulin sensitivity.
- Insulin-mediated vasodilation relies on nitric oxide.
- Previous evidence suggests nitric oxide inhibition may impair insulin sensitivity.
Purpose of the Study:
- To investigate the direct effects of systemic nitric oxide synthase inhibition on insulin sensitivity and skeletal muscle blood flow in humans.
- To test the hypothesis that inhibiting nitric oxide reduces insulin sensitivity.
Main Methods:
- A randomized, double-blind, placebo-controlled, crossover study involving 16 healthy males.
- Systemic nitric oxide synthase inhibition using NG-monomethyl L-arginine (NMA).
- Assessment of whole-body glucose uptake via euglycaemic hyperinsulinaemic clamp and calf blood flow using venous occlusion plethysmography.
Main Results:
- NMA infusion caused a pressor effect and a negative chronotropic response.
- Whole-body glucose uptake significantly increased following NMA infusion (P = 0.036).
- Calf blood flow was also significantly elevated with NMA compared to placebo (P < 0.05).
Conclusions:
- Systemic inhibition of nitric oxide synthesis paradoxically increases whole-body glucose uptake.
- Increased skeletal muscle blood flow following NMA may mediate the enhanced glucose uptake.
- These findings challenge the established link between nitric oxide inhibition and decreased insulin sensitivity.