Insulin inhibits tumor necrosis factor-α induction in myocardial ischemia/reperfusion: Role of Akt and endothelial nitric oxide synthase phosphorylation*

Li, Jingya; Hf, Zhang; Wu, Feng; Nan, Ying; Ma, Heng; W, Guo; Wang, Haichang; Ren, Jun; Das, Undurti N.; Gao, Feng

doi:10.1097/ccm.0b013e3181782335

Cited by 76 publications

(54 citation statements)

References 37 publications

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“…Endothelial-derived NO can inhibit the expression of TNF-α and other pro-inflammatory factors. In addition, endothelial-derived NO can increase the expression levels of IL-10 and other anti-inflammatory factors, and indirectly inhibit aggregation of inflammatory cells during local inflammation, thereby reducing the inflammatory response (41). In the present study, administration of L-NAME, a nitric oxide synthase inhibitor, abolished the protective effect of Res.…”

mentioning

confidence: 56%

Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway

Xie

Zhuang

et al. 2014

Mol Med Report

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Abstract. It has been previously reported that Toll-like receptor 4 (TLR4)/NF-κB signaling mediates early inflammation during myocardial ischemia and reperfusion. It has additionally been suggested that resveratrol produces cardioprotective and anti-inflammatory effects. The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF-κB signaling, reduce neutrophil accumulation and TNF-α induction in an ischemia/reperfusion injured rat heart model. Rats were randomly exposed to a sham operation, myocardial ischemia and reperfusion (MI/R), MI/R + resveratrol or MI/R + resveratrol + L-NAME. The data showed that following MI/R, the expression of myocardial TLR4 and NF-κB increased significantly in the area of induced ischemia. As compared with MI/R, resveratrol significantly attenuated the expression of TLR4 and NF-κB and reduced the levels of myeloperoxidase, serum and myocardial TNF-α production, myocardial infarct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L-NAME, a nitric oxide (NO) synthase inhibitor. These data provide evidence that resveratrol inhibits TLR4/NF-κB signaling in the rat heart subjected to MI/R, and the anti-inflammatory effect of resveratrol is associated with NO production.

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mentioning

confidence: 56%

Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway

Xie

Zhuang

et al. 2014

Mol Med Report

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“…Among all the pro-inflammatory cytokines, TNF-α is the most active one in triggering the production of other cytokines such as IL-6 and other expression molecules [16] . We provided direct evidence in myocardial ischemia/reperfusion (I/R) rats that insulin inhibits TNF-α induction locally and systemically, and demonstrated for the first time that in vitro treatment with insulin attenuated I/R-induced TNF-α production in cardiomyocytes via the Akt-eNOS-NO signaling pathway [17] . Polymorphonuclear neutrophils (PMN) are the first defense line against infection and invasive microorganisms.…”

Section: Mediatorsmentioning

confidence: 99%

New insights into insulin: The anti-inflammatory effect and its clinical relevance

Sun

Gao

2014

WJD

Self Cite

202

132

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Hyperglycemia, a commonly exhibited metabolic disorder in critically ill patients, activates the body's inflammatory defense mechanism, causing the waterfall release of numerous inflammatory mediators and cytokines, and eventually leads to organ damage. As the only glucose-lowering hormone in the body, insulin not only alleviates the detrimental effects of hyperglycemia through its metabolic regulation, but also directly modulates inflammatory mediators and acts upon immune cells to enhance immunocompetence. In this sense, hyperglycemia is pro-inflammatory whereas insulin is anti-inflammatory. Therefore, during the past 50 years, insulin has not only been used in the treatment of diabetes, but has also been put into practical use in dealing with cardiovascular diseases and critical illnesses. This review summarizes the recent advances regarding the anti-inflammatory effects of insulin in both basic research and clinical trials, with the hope of aiding in the design of further experimental research and promoting effective insulin administration in clinical practice.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved. Key words: Insulin; Inflammation; HyperglycemiaCore tip: Hyperglycemia is closely correlated with poor outcomes of morbidity and mortality in critically ill patients. As the only glucose-lowering hormone in the body, insulin not only alleviates the detrimental effects of hyperglycemia through its metabolic regulation, but also directly modulates inflammatory mediators and acts upon immune cells to enhance immunocompetence. This review summarizes the recent advances regarding the anti-inflammatory effects of insulin from our laboratory as well as others, in the hope of leading to a better understanding of this old, classic and wonder hormone and its wider and effective applications in clinical practice.Sun Q, Li J, Gao F. New insights into insulin: The antiinflammatory effect and its clinical relevance. World J Diabetes 2014; 5(2): 89-96 Available from:

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“…Myocardial depressant factors such as TNF-α, IL-1β, and nitric oxide (24)(25)(26) and ineffective metabolism by increased free fatty acids (27) may contribute to septic myocardial depression. Insulin appears to suppress the secretion and antagonize the harmful effects of TNF-α, macrophage migration inhibitory factor, and superoxide anion (28)(29)(30) and increase anti-inflammatory signal transduction (31)(32)(33). Furthermore, insulin has been found to suppress free fatty acids and increase the utilization of glucose, providing an efficient energy source (34,35).…”

Section: Discussionmentioning

confidence: 99%

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

et al. 2016

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Insulin inhibits tumor necrosis factor-α induction in myocardial ischemia/reperfusion: Role of Akt and endothelial nitric oxide synthase phosphorylation*

Cited by 76 publications

References 37 publications

Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway

Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway

New insights into insulin: The anti-inflammatory effect and its clinical relevance

Glucose-insulin-potassium correlates with hemodynamic improvement in patients with septic myocardial dysfunction

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