April - June 2008, Volume 4, Issue 2

Koshinatam K, Oshida Y, Kubota M, Sato Y

Exposure to nitric oxide does not induce insulin resistance of glucose uptake in isolated rat epitrochlearis muscle

Acta Endo (Buc) 2008, 4 (2): 133-142
doi: 10.4183/aeb.2008.133

Accumulating evidence indicates that induction of inducible nitric oxide (NO) synthase and the subsequent NO production may be involved in the pathogenesis of insulin resistance. However the role of NO on insulin action of glucose uptake in skeletal muscle is not clearly understood. We hypothesized that NO does not impair insulin action of glucose uptake in skeletal muscle. To test this hypothesis, isolated rat epitrochlearis muscles were incubated in the presence or absence of sodium nitroprusside (SNP), a NO donor, with or without insulin, followed by measurement of glucose uptake. A low concentration of SNP (0.1 mM) did not stimulate glucose uptake, whereas a high concentration of SNP (10 mM) caused a large increase in glucose uptake in the absence of insulin (basal: 1.08?0.13; 0.1mM SNP: 1.32?0.11; 10 mM SNP:3.85?0.32 μmol/ml/20 min) When muscles were incubated in the presence of 0.1 mM SNP with insulin, the glucose uptake was not significantly different than that induced by insulin alone (insulin: 3.54?0.34; insulin+0.1mM SNP: 4.42?0.37 μmol/ml/20 min). In the presence of 10 mM SNP with insulin, the combined effect on glucose uptake was greater than that induced by insulin alone (insulin+10mM SNP: 6.32 ? 0.31 μmol/ml/20 min). The calculation of net increase of insulinstimulated glucose uptake (SNP+insulin minus SNP alone) clearly demonstrated that insulin action of glucose uptake was not impaired by SNP. Furthermore, wortmannin did not inhibit SNPstimulated glucose uptake and NG-monomethyl-L-arginine, a NO synthase (NOS) inhibitor, also did not block insulin-stimulated glucose uptake, indicating no interaction between NO signaling and insulin signaling in glucose uptake mechanisms. These results strongly suggest that NO does not induce insulin resistance of glucose uptake in isolated rat epitrochlearis muscle.

Keywords: Nitric oxide, insulin action, skeletal muscle, rat

Correspondence: Yoshiharu Oshida, MD, PhD, Research Center of Health, Physical Fitness and Sports, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan, Phone:81-52-789- 3961, Fax: 81-52-789-3957, E-mail: oshida@htc.nagoya-u.ac.jp