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SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction
Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD(+)-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411148/ https://www.ncbi.nlm.nih.gov/pubmed/25915406 http://dx.doi.org/10.1371/journal.pone.0124744 |
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author | Kim, Min Lee, Ji Seon Oh, Joo En Nan, Jinyan Lee, Hakmo Jung, Hye Seung Chung, Sung Soo Park, Kyong Soo |
author_facet | Kim, Min Lee, Ji Seon Oh, Joo En Nan, Jinyan Lee, Hakmo Jung, Hye Seung Chung, Sung Soo Park, Kyong Soo |
author_sort | Kim, Min |
collection | PubMed |
description | Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD(+)-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether SIRT3 overexpression affects palmitate-induced β-cell dysfunction in cells of line NIT1, which are derived from mouse pancreatic β-cells. Two different lengths of SIRT3 were overexpressed: full length SIRT3 (SIRT3LF), which was preferentially targeted to mitochondria and partially to the nucleus, and its N-terminal truncated form (SIRT3SF), which was located in the nucleus and cytoplasm. Overexpression of SIRT3LF and SIRT3SF using an adenoviral system alleviated palmitate-induced lipotoxicity such as reduction of cell viability and mitogen-activated protein kinase (MAPK) activation. Chronic exposure to low concentrations of palmitate suppressed glucose-stimulated insulin secretion, but the suppression was effectively reversed by overexpression of SIRT3LF or SIRT3SF. The mRNA levels of the endoplasmic reticulum (ER) stress responsive genes ATF4, GRP94 and FKBP11 were increased by palmitate treatment, but the increases were completely inhibited by SIRT3LF overexpression and less effectively inhibited by SIRT3SF overexpression. This result suggests that overexpression of SIRT3 inhibits induction of ER stress by palmitate. Collectively, we conclude that overexpression of SIRT3 alleviates palmitate-induced β-cell dysfunction. |
format | Online Article Text |
id | pubmed-4411148 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-44111482015-05-07 SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction Kim, Min Lee, Ji Seon Oh, Joo En Nan, Jinyan Lee, Hakmo Jung, Hye Seung Chung, Sung Soo Park, Kyong Soo PLoS One Research Article Abnormally high levels of circulating free fatty acids can lead to pancreatic islet β-cell dysfunction and apoptosis, contributing to β-cell failure in Type 2 diabetes. The NAD(+)-dependent protein deacetylase Sirtuin-3 (SIRT3) has been implicated in Type 2 diabetes. In this study, we tested whether SIRT3 overexpression affects palmitate-induced β-cell dysfunction in cells of line NIT1, which are derived from mouse pancreatic β-cells. Two different lengths of SIRT3 were overexpressed: full length SIRT3 (SIRT3LF), which was preferentially targeted to mitochondria and partially to the nucleus, and its N-terminal truncated form (SIRT3SF), which was located in the nucleus and cytoplasm. Overexpression of SIRT3LF and SIRT3SF using an adenoviral system alleviated palmitate-induced lipotoxicity such as reduction of cell viability and mitogen-activated protein kinase (MAPK) activation. Chronic exposure to low concentrations of palmitate suppressed glucose-stimulated insulin secretion, but the suppression was effectively reversed by overexpression of SIRT3LF or SIRT3SF. The mRNA levels of the endoplasmic reticulum (ER) stress responsive genes ATF4, GRP94 and FKBP11 were increased by palmitate treatment, but the increases were completely inhibited by SIRT3LF overexpression and less effectively inhibited by SIRT3SF overexpression. This result suggests that overexpression of SIRT3 inhibits induction of ER stress by palmitate. Collectively, we conclude that overexpression of SIRT3 alleviates palmitate-induced β-cell dysfunction. Public Library of Science 2015-04-27 /pmc/articles/PMC4411148/ /pubmed/25915406 http://dx.doi.org/10.1371/journal.pone.0124744 Text en © 2015 Kim 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 Kim, Min Lee, Ji Seon Oh, Joo En Nan, Jinyan Lee, Hakmo Jung, Hye Seung Chung, Sung Soo Park, Kyong Soo SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title | SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title_full | SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title_fullStr | SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title_full_unstemmed | SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title_short | SIRT3 Overexpression Attenuates Palmitate-Induced Pancreatic β-Cell Dysfunction |
title_sort | sirt3 overexpression attenuates palmitate-induced pancreatic β-cell dysfunction |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4411148/ https://www.ncbi.nlm.nih.gov/pubmed/25915406 http://dx.doi.org/10.1371/journal.pone.0124744 |
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