Effect of Nitrate on Gene and Protein Expression of NOS Enzymes 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.