Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans

• DOI: 10.2337/dc10-0929
• Publication Date: 2010-08-11T05:52:23Z
• Authors: Paresh Dandona; Husam Ghanim; Arindam Bandyopad...; Kelly Korzeniewski; Chang Ling Sia; Sandeep Dhindsa; Ajay Chaudhuri
• Keywords: TBARS; Resistin; Lipopolysaccharide binding protein; Thiobarbituric acid

OBJECTIVE To investigate whether insulin reduces the magnitude of oxidative, nitrosative, and inflammatory stress tissue damage responses induced by endotoxin (lipopolysaccharide [LPS]). RESEARCH DESIGN AND METHODS Nine normal subjects were injected intravenously with 2 ng/kg LPS prepared from Escherichia coli. Ten others infused (2 units/h) for 6 h in addition to injection along 100 ml/h 5% dextrose maintain normoglycemia. RESULTS a rapid increase plasma concentrations nitric oxide metabolites, nitrite nitrate (NOM), thiobarbituric acid–reacting substances (TBARS), an reactive oxygen species (ROS) generation polymorphonuclear leukocytes (PMNLs), marked increases free fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibition factor (MIF), C-reactive protein, resistin, visfatin, lipopolysaccharide binding protein (LBP), high mobility group-B1 (HMG-B1), myoglobin concentrations. The coinfusion led total elimination NOM, TBARS significant reduction ROS PMNLs MIF, Insulin did not affect TNF-α, MCP-1, IL-6, LBP, HMG-B1 LPS. CONCLUSIONS significantly several key mediators These effects require further investigation its potential use as anti-inflammatory therapy endotoxemia.