Regulation of Inducible Nitric Oxide Synthase (iNOS) and its Potential Role in Insulin Resistance, Diabetes and Heart Failure

Sanja S Soskić1, Branislava D Dobutović1, Emina M Sudar1, Milan M Obradović1, Dragana M Nikolić1, Jelena D Djordjevic2, Djordje J Radak3, Dimitri P Mikhailidis4, Esma R Isenović1, *
1 Laboratory for Radiobiology and Molecular Genetics, Institute "Vinča", University of Belgrade, Serbia
2 Institute of Physiology and Biochemistry, Faculty of Biology, University of Belgrade, Studentski trg 16, 11000 Belgrade, P.O.Box S2 Republic of Serbia
3 Department of Vascular Surgery, Dedinje Cardiovascular Institute, Belgrade University School of Medicine, Belgrade, Serbia
4 Department of Clinical Biochemistry (Vascular Disease Prevention Clinics), Royal Free campus, University College London Medical School, University College London (UCL), Pond Street, London NW3 2QG, UK

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© Soskić et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Institute Vinca, University of Belgrade, Laboratory for Radiobiology and Molecular Genetics, P.O.Box 522,11000 Belgrade, Serbia; Tel/Fax: +38111-8066868; E-mail:


Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a reactive oxygen species as well as a reactive nitrogen species. It is a free radical which mediates several biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are regulated and extend to almost every cell type and function within the circulation. In mammals 3 distinct isoforms of NOS have been identified: neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS). The important isoform in the regulation of insulin resistance (IR) is iNOS. Understanding the molecular mechanisms regulating the iNOS pathway in normal and hyperglycemic conditions would help to explain some of vascular abnormalities observed in type 2 diabetes mellitus (T2DM). Previous studies have reported increased myocardial iNOS activity and expression in heart failure (HF). This review considers the recent animal studies which focus on the understanding of regulation of iNOS activity/expression and the role of iNOS agonists as potential therapeutic agents in treatment of IR, T2DM and HF.

Keywords: Inducible nitric oxide synthase, insulin resistance, diabetes, heart failure..