Although the role of
nitric oxide (NO) in peripheral
glucose uptake has been thoroughly described, little is known regarding the alterations in NO metabolism during the early onset of
insulin resistance. During this study we investigated the alterations in NO synthesis and bioavailability in a model for dietary modulations of
insulin sensitivity. For 6 weeks, rats were fed a standard diet (C), a high-
sucrose diet inducing
insulin resistance (HS), or high-
sucrose diets supplemented with
cysteine, which endowed protection against the high-
sucrose-induced
insulin resistance (Ti). Several markers of NO synthesis and bioavailability were assessed and confronted with markers of
insulin sensitivity. After 5 weeks, although urinary cGMP excretion did not differ between the groups,
insulin resistance in HS rats was associated with both a significant increase in NO oxidation, as determined by plasma
nitrotyrosine concentrations, and in the inducible
NO synthase (iNOS)/endothelial
NO synthase (iNOS/eNOS)
mRNA ratio in skeletal muscle compared with C rats. These alterations were prevented in rats fed the
cysteine-rich diets. NO production, as assessed by urinary 15NO3* excretion following a [15N2-(guanido)]-
arginine intra-venous bolus, independently and significantly correlated with
insulin sensitivity but did not significantly differ between C, HS, and Ti rats; neither did the aortic eNOS
protein expression or skeletal muscle
insulin-induced eNOS activation. Our results indicate that in this model of dietary modulations of
insulin sensitivity (i) NO production accounts for part of total inter-individual variation in
insulin sensitivity, but (ii) early diet-related changes in
insulin sensitivity are accompanied by changes in NO bioavailability.