PMID- 34161215 OWN - NLM STAT- MEDLINE DCOM- 20220404 LR - 20220405 IS - 2212-3873 (Electronic) IS - 1871-5303 (Linking) VI - 21 IP - 12 DP - 2021 TI - Effect of Nitrate on Gene and Protein Expression of Nitric Oxide Synthase Enzymes in Insulin-Sensitive Tissues of Type 2 Diabetic Male Rats. PG - 2220-2230 LID - 10.2174/1871530321666210622155649 [doi] AB - 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. CI - Copyright(c) Bentham Science Publishers; For any queries, please email at epub@benthamscience.net. FAU - Shokri, Majid AU - Shokri M AD - School of Biology, Damghan University, Damghan,Iran. FAU - Jeddi, Sajad AU - Jeddi S AD - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran,Iran. FAU - Faridnouri, Hassan AU - Faridnouri H AD - School of Biology, Damghan University, Damghan,Iran. FAU - Khorasani, Vajiheh AU - Khorasani V AD - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran,Iran. FAU - Kashfi, Khosrow AU - Kashfi K AD - Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, New York,United States. FAU - Ghasemi, Asghar AU - Ghasemi A AD - Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran,Iran. LA - eng GR - 18012/Research Institute for Endocrine Sciences (RIES) of Shahid Beheshti University of Medical Sciences/ PT - Journal Article PL - United Arab Emirates TA - Endocr Metab Immune Disord Drug Targets JT - Endocrine, metabolic & immune disorders drug targets JID - 101269157 RN - 0 (Insulin) RN - 0 (Nitrates) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.13.39 (Nitric Oxide Synthase) SB - IM MH - Animals MH - *Diabetes Mellitus, Experimental/drug therapy/genetics/metabolism MH - *Diabetes Mellitus, Type 2/drug therapy/metabolism MH - Insulin MH - Male MH - Nitrates MH - Nitric Oxide MH - Nitric Oxide Synthase/metabolism MH - Rats OTO - NOTNLM OT - Insulin-sensitive tissues OT - NO3- OT - Nitric oxide synthase OT - Rat OT - Type 2 diabetes EDAT- 2021/06/24 06:00 MHDA- 2022/04/05 06:00 CRDT- 2021/06/23 17:16 PHST- 2020/11/29 00:00 [received] PHST- 2021/03/06 00:00 [revised] PHST- 2021/03/22 00:00 [accepted] PHST- 2021/06/24 06:00 [pubmed] PHST- 2022/04/05 06:00 [medline] PHST- 2021/06/23 17:16 [entrez] AID - EMIDDT-EPUB-116281 [pii] AID - 10.2174/1871530321666210622155649 [doi] PST - ppublish SO - Endocr Metab Immune Disord Drug Targets. 2021;21(12):2220-2230. doi: 10.2174/1871530321666210622155649.