title: Roles of insulin, age, and asymmetric dimethylarginine on nitric oxide synthesis in vivo.
abstract: We tested the effects of insulin on production of nitrous oxide (NO)-related substances (nitrites and nitrates [NOx]) after (15)N-arginine intravenous infusion and on asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations in conditions reportedly associated with altered NO availability, i.e., aging, hypertension, hypercholesterolemia, and type 2 diabetes mellitus (T2DM). A total of 26 male subjects (age 23-71 years, BMI 23-33 kg/m(2)), some of whom were affected by mixed pathologic features, were enrolled. NOx fractional synthesis rate (FSR) was lower in elderly (P < 0.015) and T2DM subjects (P < 0.03) than in matched control subjects. Hyperinsulinemia generally increased both NOx FSR and absolute synthesis rate (ASR) and reduced NOx, ADMA, and SDMA concentrations. Insulin sensitivity was impaired only in T2DM. With use of simple linear regression analysis across all subjects, age was inversely correlated with both NOx FSR (R(2) = 0.23, P < 0.015) and ASR (R(2) = 0.21, P < 0.02). NOx FSR inversely correlated with both ADMA and SDMA. With use of multiple regression analysis and various models, NOx FSR remained inversely associated with age and ADMA, whereas ASR was inversely associated with age and diabetes. No association with insulin sensitivity was found. We conclude that whole-body NOx production is decreased in aging and T2DM. Age, ADMA concentration, and T2DM, but not insulin resistance, appear as negative regulators of whole-body NOx production.
authors.affiliation: Metabolism Division, Department of Medicine, University of Padova, Padova, Italy. paolo.tessari@unipd.it
authors.forename: Paolo
authors.initials: P
authors.lastname: Tessari
authors.forename: Diego
authors.initials: D
authors.lastname: Cecchet
authors.forename: Carlo
authors.initials: C
authors.lastname: Artusi
authors.forename: Monica
authors.initials: M
authors.lastname: Vettore
authors.forename: Renato
authors.initials: R
authors.lastname: Millioni
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
authors.forename: Lucia
authors.initials: L
authors.lastname: Puricelli
authors.forename: Monica
authors.initials: M
authors.lastname: Vedovato
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000096:biosynthesis*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine