Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans.
OBJECTIVE
To investigate whether insulin reduces the magnitude of oxidative, nitrosative, and inflammatory stress and tissue damage responses induced by endotoxin (lipopolysaccharide [LPS]).


METHODS
Nine normal subjects were injected intravenously with 2 ng/kg LPS prepared from Escherichia coli. Ten others were infused with insulin (2 units/h) for 6 h in addition to the LPS injection along with 100 ml/h of 5% dextrose to maintain normoglycemia.


RESULTS
LPS injection induced a rapid increase in plasma concentrations of nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric acid-reacting substances (TBARS), an increase in reactive oxygen species (ROS) generation by polymorphonuclear leukocytes (PMNLs), and marked increases in plasma 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), and myoglobin concentrations. The coinfusion of insulin led to a total elimination of the increase in NOM, free fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and plasma MIF, visfatin, and myoglobin concentrations. Insulin did not affect TNF-α, MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.


CONCLUSIONS
Insulin reduces significantly several key mediators of oxidative, nitrosative, and inflammatory stress and tissue damage induced by LPS. These effects of insulin require further investigation for its potential use as anti-inflammatory therapy for endotoxemia.
Dandona
Paresh
P
Division of Endocrinology, Diabetes and Metabolism, State University of New York at Buffalo and Kaleida Health, Buffalo, New York, USA. pdandona@kaleidahealth.org
Ghanim
Husam
H
Bandyopadhyay
Arindam
A
Korzeniewski
Kelly
K
Ling Sia
Chang
C
Dhindsa
Sandeep
S
Chaudhuri
Ajay
A
D000209:Acute-Phase Proteins; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D004731:Endotoxins / Q000633:toxicity*; D006801:Humans; D007275:Injections, Intravenous; D007328:Insulin / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008562:Membrane Glycoproteins / Q000097:blood; D009211:Myoglobin / Q000097:blood; D054409:Nicotinamide Phosphoribosyltransferase / Q000097:blood; D009566:Nitrates / Q000097:blood; D017942:Nitric Acid / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000097:blood*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein
D000209:Acute-Phase Proteins; D002097:C-Reactive Protein; D002352:Carrier Proteins; D018932:Chemokine CCL2; D004731:Endotoxins; D007328:Insulin; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; D008562:Membrane Glycoproteins; D009211:Myoglobin; D054409:Nicotinamide Phosphoribosyltransferase; D009566:Nitrates; D017942:Nitric Acid; D009573:Nitrites; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D000099231:Lipopolysaccharide-Binding Protein