Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782270714244497408 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3661618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT koppakasudha reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT kehlenbrinksylvia reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT careymichelle reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT liweijie reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT sanchezelizabeth reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT leedoeun reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT leehanna reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT chenjulie reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT carrascoemilce reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT kishorepreeti reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT zhangkehao reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans AT hawkinsmeredith reducedadiposetissuemacrophagecontentisassociatedwithimprovedinsulinsensitivityinthiazolidinedionetreateddiabetichumans |