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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2014
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.
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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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