PMID- 18040070 OWN - NLM STAT- MEDLINE DCOM- 20071227 LR - 20151119 IS - 1535-3702 (Print) IS - 1535-3699 (Linking) VI - 232 IP - 11 DP - 2007 Dec TI - Nitric oxide bioavailability and not production is first altered during the onset of insulin resistance in sucrose-fed rats. PG - 1458-64 AB - 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. FAU - Blouet, Clemence AU - Blouet C AD - INRA, AgroParisTech, UMR914 Nutrition Physiology and Ingestive Behavior, Centre de Recherche en Nutrition Humaine-Ile de France, 75005 Paris, France. FAU - Mariotti, Francois AU - Mariotti F FAU - Mathe, Veronique AU - Mathe V FAU - Tome, Daniel AU - Tome D FAU - Huneau, Jean-Francois AU - Huneau JF LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Switzerland TA - Exp Biol Med (Maywood) JT - Experimental biology and medicine (Maywood, N.J.) JID - 100973463 RN - 0 (Biomarkers) RN - 0 (Nitrates) RN - 0 (Sweetening Agents) RN - 31C4KY9ESH (Nitric Oxide) RN - 3604-79-3 (3-nitrotyrosine) RN - 42HK56048U (Tyrosine) RN - 57-50-1 (Sucrose) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type II) RN - EC 1.14.13.39 (Nitric Oxide Synthase Type III) RN - EC 1.14.13.39 (Nos2 protein, rat) RN - EC 1.14.13.39 (Nos3 protein, rat) RN - H2D2X058MU (Cyclic GMP) RN - K848JZ4886 (Cysteine) SB - IM EIN - Exp Biol Med (Maywood). 2008 Apr;233(4):492 MH - Animals MH - Aorta/enzymology MH - Biomarkers/blood/urine MH - Cyclic GMP/urine MH - Cysteine/pharmacology MH - Diet MH - Diet Therapy MH - Disease Models, Animal MH - Enzyme Activation/drug effects MH - Gene Expression Regulation, Enzymologic/*drug effects MH - *Insulin Resistance MH - Male MH - Muscle, Skeletal/enzymology MH - Muscle, Smooth, Vascular/enzymology MH - Nitrates/urine MH - Nitric Oxide/*biosynthesis MH - Nitric Oxide Synthase Type II/*biosynthesis MH - Nitric Oxide Synthase Type III MH - Rats MH - Rats, Wistar MH - Sucrose/pharmacology/*toxicity MH - Sweetening Agents/pharmacology/*toxicity MH - Tyrosine/analogs & derivatives/blood EDAT- 2007/11/28 09:00 MHDA- 2007/12/28 09:00 CRDT- 2007/11/28 09:00 PHST- 2007/11/28 09:00 [pubmed] PHST- 2007/12/28 09:00 [medline] PHST- 2007/11/28 09:00 [entrez] AID - 232/11/1458 [pii] AID - 10.3181/0703-RM-64 [doi] PST - ppublish SO - Exp Biol Med (Maywood). 2007 Dec;232(11):1458-64. doi: 10.3181/0703-RM-64.