EFFECT OF SNP AND L-NAME ON CONTRACTION, HYPOXIA, AND INSULIN STIMULATED GLUCOSE TRANSPORT ACTIVITY IN RAT SKELETAL MUSCLE

Abstract

1358 Previous studies suggest that exercise and insulin stimulate glucose transport activity (GT) in skeletal muscle through different pathways, while hypoxia and exercise stimulate GT by the same mechanism. Recently, nitric oxide (NO) is also shown to stimulate GT in skeletal muscle. Therefore, we thought it worthwhile to study relationships between NO-stimulated GT and other established physiological stimuli-increased GT in isolated rat epitrochlearis muscle. Maximal effects of contraction (15 10-s tetani) and NO-donor of 10 mM sodium nitropirusside (SNP) on GT in the muscle was additive, while maximal effects of hypoxia (90 min) and insulin (2mU/ml) on GT was not additive to the maximal effect of SNP on GT. The nitric oxide synthase inhibitor, NG-nitoro-arginine-methyl ester (L-NAME, 10mmol/l), inhibited the maximal effects of contraction and insulin on GT by 38 and 45%, respectively (p<0.05). However, GT stimulated maximally by hypoxia was not inhibited at all. In addition, SNP stimulated GT was inhibited (38%, p<0.05) by 1 μM wortmannin that is reported to totally depress insulin stimulated GT pathway by inhibiting PI-3 kinase. These results may suggest that NO and insulin stimulate GT in rat skeletal muscle through similar mechanism. Furthermore, since our results demonstrated that, regarding GT, contraction and hypoxia responded differently to NO-related pharmacological stimuli, these two GT-stimulating pathways might have a step(s) affected differently by NO-related mechanisms.