Cargando…

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]). RESEARCH DESIGN AND METHODS: Nine normal subjects were injected intravenously with 2 ng/kg LPS prepared from...

Descripción completa

Detalles Bibliográficos
Autores principales: Dandona, Paresh, Ghanim, Husam, Bandyopadhyay, Arindam, Korzeniewski, Kelly, Ling Sia, Chang, Dhindsa, Sandeep, Chaudhuri, Ajay
Formato: Texto
Lenguaje:English
Publicado: American Diabetes Association 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963505/
https://www.ncbi.nlm.nih.gov/pubmed/20699433
http://dx.doi.org/10.2337/dc10-0929
_version_ 1782189278050123776
author Dandona, Paresh
Ghanim, Husam
Bandyopadhyay, Arindam
Korzeniewski, Kelly
Ling Sia, Chang
Dhindsa, Sandeep
Chaudhuri, Ajay
author_facet Dandona, Paresh
Ghanim, Husam
Bandyopadhyay, Arindam
Korzeniewski, Kelly
Ling Sia, Chang
Dhindsa, Sandeep
Chaudhuri, Ajay
author_sort Dandona, Paresh
collection PubMed
description 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-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.
format Text
id pubmed-2963505
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher American Diabetes Association
record_format MEDLINE/PubMed
spelling pubmed-29635052011-11-01 Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans Dandona, Paresh Ghanim, Husam Bandyopadhyay, Arindam Korzeniewski, Kelly Ling Sia, Chang Dhindsa, Sandeep Chaudhuri, Ajay Diabetes Care Original Research 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-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. American Diabetes Association 2010-11 2010-08-10 /pmc/articles/PMC2963505/ /pubmed/20699433 http://dx.doi.org/10.2337/dc10-0929 Text en © 2010 by the American Diabetes Association. https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ (https://creativecommons.org/licenses/by-nc-nd/3.0/) for details.
spellingShingle Original Research
Dandona, Paresh
Ghanim, Husam
Bandyopadhyay, Arindam
Korzeniewski, Kelly
Ling Sia, Chang
Dhindsa, Sandeep
Chaudhuri, Ajay
Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title_full Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title_fullStr Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title_full_unstemmed Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title_short Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans
title_sort insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory stress in humans
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963505/
https://www.ncbi.nlm.nih.gov/pubmed/20699433
http://dx.doi.org/10.2337/dc10-0929
work_keys_str_mv AT dandonaparesh insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT ghanimhusam insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT bandyopadhyayarindam insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT korzeniewskikelly insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT lingsiachang insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT dhindsasandeep insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans
AT chaudhuriajay insulinsuppressesendotoxininducedoxidativenitrosativeandinflammatorystressinhumans