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Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans

Obesity is associated with increased adipose tissue macrophage (ATM) infiltration, and rodent studies suggest that inflammatory factors produced by ATMs contribute to insulin resistance and type 2 diabetes. However, a relationship between ATM content and insulin resistance has not been clearly estab...

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Autores principales: Koppaka, Sudha, Kehlenbrink, Sylvia, Carey, Michelle, Li, Weijie, Sanchez, Elizabeth, Lee, Do-Eun, Lee, Hanna, Chen, Julie, Carrasco, Emilce, Kishore, Preeti, Zhang, Kehao, Hawkins, Meredith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661618/
https://www.ncbi.nlm.nih.gov/pubmed/23349486
http://dx.doi.org/10.2337/db12-0868
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author Koppaka, Sudha
Kehlenbrink, Sylvia
Carey, Michelle
Li, Weijie
Sanchez, Elizabeth
Lee, Do-Eun
Lee, Hanna
Chen, Julie
Carrasco, Emilce
Kishore, Preeti
Zhang, Kehao
Hawkins, Meredith
author_facet Koppaka, Sudha
Kehlenbrink, Sylvia
Carey, Michelle
Li, Weijie
Sanchez, Elizabeth
Lee, Do-Eun
Lee, Hanna
Chen, Julie
Carrasco, Emilce
Kishore, Preeti
Zhang, Kehao
Hawkins, Meredith
author_sort Koppaka, Sudha
collection PubMed
description Obesity is associated with increased adipose tissue macrophage (ATM) infiltration, and rodent studies suggest that inflammatory factors produced by ATMs contribute to insulin resistance and type 2 diabetes. However, a relationship between ATM content and insulin resistance has not been clearly established in humans. Since thiazolidinediones attenuate adipose tissue inflammation and improve insulin sensitivity, we examined the temporal relationship of the effects of pioglitazone on these two parameters. The effect of 10 and 21 days of pioglitazone treatment on insulin sensitivity in 26 diabetic subjects was assessed by hyperinsulinemic-euglycemic clamp studies. Because chemoattractant factors, cytokines, and immune cells have been implicated in regulating the recruitment of ATMs, we studied their temporal relationship to changes in ATM content. Improved hepatic and peripheral insulin sensitivity was seen after 21 days of pioglitazone. We found early reductions in macrophage chemoattractant factors after only 10 days of pioglitazone, followed by a 69% reduction in ATM content at 21 days and reduced ATM activation at both time points. Although markers for dendritic cells and neutrophils were reduced at both time points, there were no significant changes in regulatory T cells. These results are consistent with an association between adipose macrophage content and systemic insulin resistance in humans.
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spelling pubmed-36616182014-06-01 Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans Koppaka, Sudha Kehlenbrink, Sylvia Carey, Michelle Li, Weijie Sanchez, Elizabeth Lee, Do-Eun Lee, Hanna Chen, Julie Carrasco, Emilce Kishore, Preeti Zhang, Kehao Hawkins, Meredith Diabetes Original Research Obesity is associated with increased adipose tissue macrophage (ATM) infiltration, and rodent studies suggest that inflammatory factors produced by ATMs contribute to insulin resistance and type 2 diabetes. However, a relationship between ATM content and insulin resistance has not been clearly established in humans. Since thiazolidinediones attenuate adipose tissue inflammation and improve insulin sensitivity, we examined the temporal relationship of the effects of pioglitazone on these two parameters. The effect of 10 and 21 days of pioglitazone treatment on insulin sensitivity in 26 diabetic subjects was assessed by hyperinsulinemic-euglycemic clamp studies. Because chemoattractant factors, cytokines, and immune cells have been implicated in regulating the recruitment of ATMs, we studied their temporal relationship to changes in ATM content. Improved hepatic and peripheral insulin sensitivity was seen after 21 days of pioglitazone. We found early reductions in macrophage chemoattractant factors after only 10 days of pioglitazone, followed by a 69% reduction in ATM content at 21 days and reduced ATM activation at both time points. Although markers for dendritic cells and neutrophils were reduced at both time points, there were no significant changes in regulatory T cells. These results are consistent with an association between adipose macrophage content and systemic insulin resistance in humans. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661618/ /pubmed/23349486 http://dx.doi.org/10.2337/db12-0868 Text en © 2013 by the American Diabetes Association. 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/ for details.
spellingShingle Original Research
Koppaka, Sudha
Kehlenbrink, Sylvia
Carey, Michelle
Li, Weijie
Sanchez, Elizabeth
Lee, Do-Eun
Lee, Hanna
Chen, Julie
Carrasco, Emilce
Kishore, Preeti
Zhang, Kehao
Hawkins, Meredith
Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title_full Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title_fullStr Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title_full_unstemmed Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title_short Reduced Adipose Tissue Macrophage Content Is Associated With Improved Insulin Sensitivity in Thiazolidinedione-Treated Diabetic Humans
title_sort reduced adipose tissue macrophage content is associated with improved insulin sensitivity in thiazolidinedione-treated diabetic humans
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661618/
https://www.ncbi.nlm.nih.gov/pubmed/23349486
http://dx.doi.org/10.2337/db12-0868
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