Insulin sensitivity and resistin expression in nitric oxide-deficient rats
C-C Juan, C-L Chang, D-Y Chung, S-W Huang, C-F Kwok, L-T Ho
Department of Physiology, School of Medicine, National Yang-Ming University, and Department of Medical Research & Education, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
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Aims/hypothesis: The purpose of this study was to investigate the changes in insulin sensitivity and adipocyte resistin expression in long-term nitric oxide (NO)-deficient rats.
Methods: Male Sprague-Dawley rats received Nw-nitro-L-arginine methyl ester (L-NAME; 0.5 mg/mL) in their drinking water for four weeks, while controls received plain drinking water. During the experimental period, changes in plasma glucose, insulin, and C-peptide levels were measured. After 4-week L-NAME administration, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte resistin mRNA levels were examined using Northern blots.
Results: Successful induction of NO deficiency was demonstrated by an increase in the systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared to the controls, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats. Insulin sensitivity was significantly increased in NO-deficient rats. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocytes resistin mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats and the resistin mRNA levels were negatively correlated with insulin sensitivity.
Conclusion/interpretation: Insulin sensitivity was increased in NO-deficient rats and that this was associated with insulin binding capacity and downregulated resistin expression. These findings suggest that NO played a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.