Role of iNOS in Insulin Resistance and Endothelial Dysfunction

  • Hobby Aggarwal
  • Babu Nageswararao Kanuri
  • Madhu Dikshit


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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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Hobby Aggarwal
    • 1
  • Babu Nageswararao Kanuri
    • 1
    • 2
  • Madhu Dikshit
    • 3
  1. 1.Pharmacology DivisionCSIR-Central Drug Research InstituteLucknowIndia
  2. 2.Division of Endocrinology, Diabetes and MetabolismUniversity of CincinnatiCincinnatiUSA
  3. 3.Department of BiotechnologyTranslational Health Science and Technology (THSTI)FaridabadIndia

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