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Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue
Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Diabetes Association
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931405/ https://www.ncbi.nlm.nih.gov/pubmed/24130338 http://dx.doi.org/10.2337/db13-0906 |
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author | Boden, Guenther Cheung, Peter Salehi, Sajad Homko, Carol Loveland-Jones, Catherine Jayarajan, Senthil Stein, T. Peter Williams, Kevin Jon Liu, Ming-Lin Barrero, Carlos A. Merali, Salim |
author_facet | Boden, Guenther Cheung, Peter Salehi, Sajad Homko, Carol Loveland-Jones, Catherine Jayarajan, Senthil Stein, T. Peter Williams, Kevin Jon Liu, Ming-Lin Barrero, Carlos A. Merali, Salim |
author_sort | Boden, Guenther |
collection | PubMed |
description | Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼35 to ∼1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin. |
format | Online Article Text |
id | pubmed-3931405 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-39314052015-03-01 Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue Boden, Guenther Cheung, Peter Salehi, Sajad Homko, Carol Loveland-Jones, Catherine Jayarajan, Senthil Stein, T. Peter Williams, Kevin Jon Liu, Ming-Lin Barrero, Carlos A. Merali, Salim Diabetes Metabolism Endoplasmic reticulum (ER) stress is increased in obesity and is postulated to be a major contributor to many obesity-related pathologies. Little is known about what causes ER stress in obese people. Here, we show that insulin upregulated the unfolded protein response (UPR), an adaptive reaction to ER stress, in vitro in 3T3-L1 adipocytes and in vivo, in subcutaneous (sc) adipose tissue of nondiabetic subjects, where it increased the UPR dose dependently over the entire physiologic insulin range (from ∼35 to ∼1,450 pmol/L). The insulin-induced UPR was not due to increased glucose uptake/metabolism and oxidative stress. It was associated, however, with increased protein synthesis, with accumulation of ubiquitination associated proteins, and with multiple posttranslational protein modifications (acetylations, methylations, nitrosylations, succinylation, and ubiquitinations), some of which are potential causes for ER stress. These results reveal a new physiologic role of insulin and provide a putative mechanism for the development of ER stress in obesity. They may also have clinical and therapeutic implications, e.g., in diabetic patients treated with high doses of insulin. American Diabetes Association 2014-03 2014-02-13 /pmc/articles/PMC3931405/ /pubmed/24130338 http://dx.doi.org/10.2337/db13-0906 Text en © 2014 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 | Metabolism Boden, Guenther Cheung, Peter Salehi, Sajad Homko, Carol Loveland-Jones, Catherine Jayarajan, Senthil Stein, T. Peter Williams, Kevin Jon Liu, Ming-Lin Barrero, Carlos A. Merali, Salim Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title | Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title_full | Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title_fullStr | Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title_full_unstemmed | Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title_short | Insulin Regulates the Unfolded Protein Response in Human Adipose Tissue |
title_sort | insulin regulates the unfolded protein response in human adipose tissue |
topic | Metabolism |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931405/ https://www.ncbi.nlm.nih.gov/pubmed/24130338 http://dx.doi.org/10.2337/db13-0906 |
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