PMID- 20699433
OWN - NLM
STAT- MEDLINE
DCOM- 20110210
LR  - 20211020
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Print)
IS  - 0149-5992 (Linking)
VI  - 33
IP  - 11
DP  - 2010 Nov
TI  - Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory 
      stress in humans.
PG  - 2416-23
LID - 10.2337/dc10-0929 [doi]
AB  - OBJECTIVE: To investigate whether insulin reduces the magnitude of oxidative, 
      nitrosative, and inflammatory stress and 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 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-alpha (TNF-alpha), 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-alpha, 
      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.
FAU - Dandona, Paresh
AU  - Dandona P
AD  - Division of Endocrinology, Diabetes and Metabolism, State University of New York 
      at Buffalo and Kaleida Health, Buffalo, New York, USA. pdandona@kaleidahealth.org
FAU - Ghanim, Husam
AU  - Ghanim H
FAU - Bandyopadhyay, Arindam
AU  - Bandyopadhyay A
FAU - Korzeniewski, Kelly
AU  - Korzeniewski K
FAU - Ling Sia, Chang
AU  - Ling Sia C
FAU - Dhindsa, Sandeep
AU  - Dhindsa S
FAU - Chaudhuri, Ajay
AU  - Chaudhuri A
LA  - eng
GR  - R01 DK069805/DK/NIDDK NIH HHS/United States
GR  - R01 DK075877/DK/NIDDK NIH HHS/United States
GR  - R01-DK-075877/DK/NIDDK NIH HHS/United States
GR  - R01-DK-069805/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100810
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Endotoxins)
RN  - 0 (Insulin)
RN  - 0 (Interleukin-6)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Myoglobin)
RN  - 0 (Nitrates)
RN  - 0 (Nitrites)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Thiobarbituric Acid Reactive Substances)
RN  - 0 (lipopolysaccharide-binding protein)
RN  - 411VRN1TV4 (Nitric Acid)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - EC 2.4.2.12 (Nicotinamide Phosphoribosyltransferase)
SB  - IM
MH  - Acute-Phase Proteins
MH  - C-Reactive Protein/metabolism
MH  - Carrier Proteins/blood
MH  - Chemokine CCL2/blood
MH  - Endotoxins/*toxicity
MH  - Humans
MH  - Injections, Intravenous
MH  - Insulin/*therapeutic use
MH  - Interleukin-6/blood
MH  - Macrophage Migration-Inhibitory Factors/blood
MH  - Membrane Glycoproteins/blood
MH  - Myoglobin/blood
MH  - Nicotinamide Phosphoribosyltransferase/blood
MH  - Nitrates/blood
MH  - Nitric Acid/blood
MH  - Nitrites/blood
MH  - Oxidative Stress/drug effects
MH  - Reactive Oxygen Species/*blood
MH  - Thiobarbituric Acid Reactive Substances/metabolism
PMC - PMC2963505
EDAT- 2010/08/12 06:00
MHDA- 2011/02/11 06:00
PMCR- 2011/11/01
CRDT- 2010/08/12 06:00
PHST- 2010/08/12 06:00 [entrez]
PHST- 2010/08/12 06:00 [pubmed]
PHST- 2011/02/11 06:00 [medline]
PHST- 2011/11/01 00:00 [pmc-release]
AID - dc10-0929 [pii]
AID - 0929 [pii]
AID - 10.2337/dc10-0929 [doi]
PST - ppublish
SO  - Diabetes Care. 2010 Nov;33(11):2416-23. doi: 10.2337/dc10-0929. Epub 2010 Aug 10.