Bioinformatics Analysis of Functional Protein Sequences Reveals a Role for Tumor Necrosis Factor-α and Nitric Oxide in Insulin Resistance Syndrome
Appa Rao Allam,
Kodanda R.K.R. Tirumala,
Sridhar R. Gumpeny,
Suresh Babu Changalasetty,
Siva Reddy Challa,
Veera Swamy Thota,
V. V. Satyanarayana Kopparthi,
Undurt N. Das.
Using bioinformatics techniques and sequence analyses algorithms, we identified that tumor necrosis factor-α (TNF-α) and nitric oxide (NO) have a significant role in the pathobiology of insulin resistance syndrome, a condition that is common in subjects with abdominal obesity, hypertension, dyslipidemia, atherosclerosis, and coronary heart disease and are accompanied by endothelial dysfunction due to reduced endothelial nitric oxide generation. TNF-α has neurotoxic actions, stimulates inducible NO synthase activity, and modulates the expression of neurotransmitters involved in the control of feeding and thermogenesis. NO is a neurotransmitter and influences secretion and actions of various hypothalamic peptides and neuropeptides. Insulin suppresses the production of TNF-α but stimulates that of endothelial NO. This close interaction between TNF-α, NO, hypothalamic peptides, and insulin suggests that regulation of TNF-α and NO production and action could be critical in the management of insulin resistance syndrome and its associated conditions.
Keywords: Insulin resistance, tumor necrosis factor, nitric oxide, hypothalamus, neurotransmission, insulin, endothelium, inflammation
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