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An Inflammatory Cascade Leading to Hyperresistinemia in Humans
BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2004
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC529430/ https://www.ncbi.nlm.nih.gov/pubmed/15578112 http://dx.doi.org/10.1371/journal.pmed.0010045 |
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author | Lehrke, Michael Reilly, Muredach P Millington, Segan C Iqbal, Nayyar Rader, Daniel J Lazar, Mitchell A |
author_facet | Lehrke, Michael Reilly, Muredach P Millington, Segan C Iqbal, Nayyar Rader, Daniel J Lazar, Mitchell A |
author_sort | Lehrke, Michael |
collection | PubMed |
description | BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages. METHODS AND FINDINGS: The effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants. Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-κB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor α receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis. CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. |
format | Text |
id | pubmed-529430 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-5294302004-11-30 An Inflammatory Cascade Leading to Hyperresistinemia in Humans Lehrke, Michael Reilly, Muredach P Millington, Segan C Iqbal, Nayyar Rader, Daniel J Lazar, Mitchell A PLoS Med Research Article BACKGROUND: Obesity, the most common cause of insulin resistance, is increasingly recognized as a low-grade inflammatory state. Adipocyte-derived resistin is a circulating protein implicated in insulin resistance in rodents, but the role of human resistin is uncertain because it is produced largely by macrophages. METHODS AND FINDINGS: The effect of endotoxin and cytokines on resistin gene and protein expression was studied in human primary blood monocytes differentiated into macrophages and in healthy human participants. Inflammatory endotoxin induced resistin in primary human macrophages via a cascade involving the secretion of inflammatory cytokines that circulate at increased levels in individuals with obesity. Induction of resistin was attenuated by drugs with dual insulin-sensitizing and anti-inflammatory properties that converge on NF-κB. In human study participants, experimental endotoxemia, which produces an insulin-resistant state, causes a dramatic rise in circulating resistin levels. Moreover, in patients with type 2 diabetes, serum resistin levels are correlated with levels of soluble tumor necrosis factor α receptor, an inflammatory marker linked to obesity, insulin resistance, and atherosclerosis. CONCLUSIONS: Inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. Public Library of Science 2004-11 2004-11-30 /pmc/articles/PMC529430/ /pubmed/15578112 http://dx.doi.org/10.1371/journal.pmed.0010045 Text en Copyright: © 2004 Lehrke et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Lehrke, Michael Reilly, Muredach P Millington, Segan C Iqbal, Nayyar Rader, Daniel J Lazar, Mitchell A An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title | An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title_full | An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title_fullStr | An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title_full_unstemmed | An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title_short | An Inflammatory Cascade Leading to Hyperresistinemia in Humans |
title_sort | inflammatory cascade leading to hyperresistinemia in humans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC529430/ https://www.ncbi.nlm.nih.gov/pubmed/15578112 http://dx.doi.org/10.1371/journal.pmed.0010045 |
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