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Role of iNOS in Insulin Resistance and Endothelial Dysfunction

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Oxidative Stress in Heart Diseases

Abstract

Nitric oxide (NO) is an important gaseous signaling molecule with diverse roles in various physiological processes like maintenance of vascular tone, regulation of metabolism, cell apoptosis etc. NO synthesis in the body is regulated by nitric oxide synthase (NOS); primarily by Ca2+ dependent endothelial and neuronal (eNOS and nNOS), and Ca2+ independent inducible (iNOS) isoforms. Insulin resistance (IR), a critical component in the pathophysiology of lifestyle diseases such as obesity and Type 2 diabetes is characterized by hyperglycemia, dyslipidemia and is also linked to altered gut microbiome. Endothelial dysfunction in obesity and diabetes enhance the risk of cardiovascular complications such as hypertension, atherosclerosis, myocardial infarction, and cerebral stroke. iNOS, which produces high and sustained levels of NO under pathophysiological stimuli is implicated to have deleterious effects on cardiovascular system. During insulin resistant states and its associated complications, iNOS participates in deregulating tissue metabolic processes via imbalance in homeostasis of glucose and lipids as well as endothelial dysfunction through local and systemic inflammatory milieu. This is majorly a resultant of increased nitrosative stress (due to ONOO− release formed by combination of NO and O2 −) which impacts the functions of various proteins involved in maintaining the metabolism and vascular homeostasis by S-glutathionylation of cysteine and/or nitration of tyrosine residues of crucial proteins. Decreased availability of tissue NO in these diseased conditions has opened a new arena of therapeutics focusing on increasing the NO bioavailability via administration of NO precursors such as arginine, nitrite and cell permeable tetrahydrobiopterin analogs on one hand or through a search for selective iNOS inhibitors on the other. This chapter focuses on the role of iNOS in insulin resistance and endothelial functionality through its modulatory effects on tissue metabolism and inflammatory cytokines.

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Authors and Affiliations

  1. Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow, India

    Hobby Aggarwal & Babu Nageswararao Kanuri

  2. Division of Endocrinology, Diabetes and Metabolism, University of Cincinnati, Cincinnati, OH, USA

    Babu Nageswararao Kanuri

  3. Department of Biotechnology, Translational Health Science and Technology (THSTI), Faridabad, India

    Madhu Dikshit

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  1. Hobby Aggarwal
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  2. Babu Nageswararao Kanuri
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  3. Madhu Dikshit
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Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Sciences, St Boniface Hospital, Albrechtsen Research Centre, Winnipeg, MB, Canada

    Naranjan S Dhalla

  3. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Nirmal K Ganguly

  4. Translational Health Science and Technology (THSTI), Department of Biotechnology, Faridabad, India

    Madhu Dikshit

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Aggarwal, H., Kanuri, B.N., Dikshit, M. (2019). Role of iNOS in Insulin Resistance and Endothelial Dysfunction. In: Chakraborti, S., Dhalla, N., Ganguly, N., Dikshit, M. (eds) Oxidative Stress in Heart Diseases. Springer, Singapore. https://doi.org/10.1007/978-981-13-8273-4_21

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