Studies from our laboratory using acute pharmacologic blockade of nitric oxide synthase (NOS) activity have suggested that nitric oxide (NO) has an important role in regulating carbohydrate metabolism. We now report on insulin sensitivity in mice with targeted disruptions in endothelial NOS (eNOS) and neuronal NOS (nNOS) genes compared with their wild-type (WT) counterparts. Mice underwent hyperinsulinemic-euglycemic clamp studies after a 24-h fast, during an insulin infusion of 20 mU · k g -1 · min -1 . Glucose levels were measured at baseline and every 10 min during the clamp. Insulin levels were measured at baseline and at the end of the clamp study. Glucose infusion rates (GIRs) during the last 30 min of the clamp study were in a steady state. Tritiated glucose infusion was used to measure rates of endogenous glucose output (EGO) both at baseline and during steady-state euglycemia. Glucose disposal rates (GDRs) were computed from the GIR and EGO. Fasting and steady-state glucose and insulin levels were comparable in the 3 groups of mice. No differences in fasting EGO were noted between the groups. GIR was significantly reduced (37%, P = 0.001) in the eNOS knockout (KO) mice compared with the WT mice, with values for the nNOS mice being intermediate. EGO was completely suppressed in the nNOS and WT mice during insulin infusion, but not in the eNOS mice. Even so, the eNOS mice displayed significantly reduced whole-body GDRs compared with those of the WT mice ( 8 2 . 6 7 ± 10.77 vs. 103.67 ± 3.47 m g · k g -1 · min -1 , P = 0.03). eNOS KO mice are insulin resistant at the level of the liver and peripheral tissues, whereas the nNOS KO mice are insulin resistant only in the latter. These data indicate that NO plays a role in modulating insulin sensitivity and carbohydrate metabolism and that the eNOS isoform may play a dominant role relative to nNOS. Diabetes 49:XXX-XXX, 2000 N itric oxide (NO) has emerged as an important molecule with diverse biological functions. In the blood vessels, NO mediates endotheliumdependent vasodilation (1-3) in response to diverse stimuli such as shear stress (4-6), insulin (7), acetylcholine (8,9), and bradykinin (3,10). In the central nervous system (CNS) and peripheral nervous tissue, NO is an unusual neurotransmitter (11-13). NO is generated when the amino acid L-arginine is converted to citrulline by the enzyme NO synthase (NOS) (14,15). Three separate genes encode the known isoforms of NOS (16): endothelial NOS (eNOS or NOS III) and neuronal NOS (nNOS or NOS II) catalyze the constitutive production of NO in a calcium-dependent manner predominantly in the blood vessels and neural tissues, respect i v e l y. The third isoform, inducible NOS (iNOS or NOS I) is located in macrophages and catalyzes NO formation in i n flammatory cells.Intravenous administration of N G -m o n o m e t h y l -L-a r g i n i n e (L-NMMA), a competitive inhibitor of all NOS isoforms, acutely induces hypertension and insulin resistance in rats ( 1 7 ) . M o r e r e c e n t l y, we reported that acute pharm...

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This paper investigates the seismic behavior of a seismic-damaged double-deck viaduct frame pier (DVFP) strengthened with CFRP and enveloped steel, four strengthened DVFP specimens with different degrees of initial damage were tested under quasi-static cyclic loading. Based on the test results, the hysteretic behavior, the stiffness and strength degradation, crack propagation, and failure mechanism were firstly analyzed. Then, the damage indexes of the tested specimens were calculated with different models to evaluate the seismic strengthening performance. Results of this study show that CFRP and enveloped steel strengthening could effectively improve the strength and ductility of pre-damaged DVFPs. The ultimate load, the failure displacement and the displacement ductility of the moderately damaged specimen after being strengthened were found to increase by 120.74%, 35% and 32.33%, respectively. For the severely damaged specimens with CFRP and enveloped steel strengthening, the figures were 105.36%, 25.98% and 31.41%, respectively. The research results can provide reference for the hybrid strengthening application of seismic-damaged DVFP.