Increased Concentration of Nitric Oxide in Type 2 Diabetes with Insulin Resistance  

It is still controversial that a decrease in the ability of insulin to increase endothelial NO release results in impaired insulin-mediated vasodilatory response. 

Insulin resistance (IR) is a key element in the pathogenesis of NIDDM. The recent experiments on insulin-mediated vasodilatation have suggested that vascular insensitivity is a component of IR. However, it is still controversial that a decrease in the ability of insulin to increase endothelial NO release results in impaired insulin-mediated vasodilatory response. 

Plasma concentrations of NO were examined in 26 patients with NIDDM, and 78 nondiabetic volunteers during a 180 min iv infusion of insulin (25 mU/m2/min), sandostatin (60 ug/h following a bolus of 25 ug) and glucose (240 mg/m2/min). 

The test measured the efficacy of insulin in promoting disposal of the infused glucose load, in which the steady state plasma glucose (SSPG) during the 150-180min of the test was used as an index of IR. All subjects had 12h of overnight fast and no food intake during the examination. Plasma NO levels were assayed by measurement of the stable end products of their metabolism (NO2-/NO3-). Comparison of the plasma NO levels between groups were performed by Wilcoxon-Mann-Whitney test, between serial observations over time by Friedman statistics. Relationships between different variables were analyzed by Pearson correlations. Statistical significance was accepted at the p=0.05 level.  

Our results showed that there were no significant increase of NO during the insulin infusion in both the diabetic and nondiabetic groups. However, the plasma NO levels at basal and 30, 60, 120, 150 min after insulin infusion were significant higher in the diabetic group. When the nondiabetic subjects were analyzed according to their SSPG levels, there was no difference of plasma NO levels between those with SSPG > 160 mg/dl and those with SSPG < 160 mg/dl. There were no statistical difference of NO levels between those with a family history of NIDDM and those without. In the nondiabetic group, SSPG correlated with BMI, fasting insulin, triglyceride, and HDL-chol, but not with plasma NO levels.  

Conclusion: 1) Impaired insulin-mediated vasodilatation in NIDDM is not caused by the impaired ability of insulin to increase endothelial NO release. The pathogenesis probably involves impaired biological effect of NO rather than its production. 2) Altered NO pathway is not an early event in IR individuals. These changes will not be apparent until NIDDM develops. Poster at Endo 2002  [P1-81] 

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