Effect of Nitrate on Gene and Protein Expression of Nitric Oxide Synthase Enzymes in Insulin-Sensitive Tissues of Type 2 Diabetic Male Rats

Background and objective: Decreased nitric oxide (NO) bioavailability contributes to the pathophysiology of type 2 diabetes mellitus (T2DM). This study aims to determine the effects of nitrate (NO3 -) on gene and protein expression of NO synthase (NOS) enzymes in the liver, soleus muscle (SM), and epididymal adipose tissue (eAT) of rats with T2DM.

Methods: Twenty-eight male rats were divided into 4 groups: Control, diabetes, control+NO3 -, and diabetes+NO3 - (n = 7/each group). NO3 - was administered for 6 months, and mRNA and protein levels of NOS enzymes were measured at the end of the study.

Results: mRNA and protein levels of inducible NOS (iNOS) were higher in the liver (475% and 73%), SM (271% and 43%), and eAT (543% and 24%) of rats with T2DM. In the case of the endothelial NOS (eNOS), diabetic rats had lower mRNA and protein levels in the liver (26% and 24%) and SM (60% and 62%) and lower mRNA level (30%) in eAT. mRNA and protein levels of neural NOS (nNOS) were lower in SM (69% and 73%) and eAT (25% and 31%) of rats with T2DM. NO3 - administration restored disrupted iNOS and eNOS expressions to their near normal values in all the studied tissues; NO3 - also increased nNOS mRNA and protein levels in SM and eAT but decreased nNOS protein level in the liver.

Conclusion: Long-term NO3 - administration restored disrupted expression of NOS enzymes in the liver, SM, and eAT of rats with T2DM; these findings partly explain the beneficial metabolic effects of nitrate in T2DM.