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Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate
BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Korean Diabetes Association
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080567/ https://www.ncbi.nlm.nih.gov/pubmed/21537415 http://dx.doi.org/10.4093/dmj.2011.35.1.65 |
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author | Ryu, Gyeong Ryul Yoo, Jun Mo Lee, Esder Ko, Seung-Hyun Ahn, Yu-Bae Song, Ki-Ho |
author_facet | Ryu, Gyeong Ryul Yoo, Jun Mo Lee, Esder Ko, Seung-Hyun Ahn, Yu-Bae Song, Ki-Ho |
author_sort | Ryu, Gyeong Ryul |
collection | PubMed |
description | BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood. METHODS: INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours. RESULTS: The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine. CONCLUSION: Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress. |
format | Text |
id | pubmed-3080567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Korean Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-30805672011-05-02 Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate Ryu, Gyeong Ryul Yoo, Jun Mo Lee, Esder Ko, Seung-Hyun Ahn, Yu-Bae Song, Ki-Ho Diabetes Metab J Original Article BACKGROUND: Type 2 diabetes mellitus (T2DM) is often accompanied by increased levels of circulating fatty acid. Elevations in fatty acids and glucose for prolonged periods of time have been suggested to cause progressive dysfunction or apoptosis of pancreatic beta cells in T2DM. However, the precise mechanism of this adverse effect is not well understood. METHODS: INS-1 rat-derived insulin-secreting cells were exposed to 30 mM glucose and 0.25 mM palmitate for 48 hours. RESULTS: The production of reactive oxygen species increased significantly. Pancreatic and duodenal homeobox 1 (Pdx1) expression was down-regulated, as assessed by reverse transcription-polymerase chain reaction and Western blot analyses. The promoter activities of insulin and Pdx1 were also diminished. Of note, there was nucleocytoplasmic translocation of Pdx1, which was partially prevented by treatment with an antioxidant, N-acetyl-L-cysteine. CONCLUSION: Our data suggest that prolonged exposure of beta cells to elevated levels of glucose and palmitate negatively affects Pdx1 expression via oxidative stress. Korean Diabetes Association 2011-02 2011-02-28 /pmc/articles/PMC3080567/ /pubmed/21537415 http://dx.doi.org/10.4093/dmj.2011.35.1.65 Text en Copyright © 2011 Korean Diabetes Association http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Article Ryu, Gyeong Ryul Yoo, Jun Mo Lee, Esder Ko, Seung-Hyun Ahn, Yu-Bae Song, Ki-Ho Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title | Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title_full | Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title_fullStr | Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title_full_unstemmed | Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title_short | Decreased Expression and Induced Nucleocytoplasmic Translocation of Pancreatic and Duodenal Homeobox 1 in INS-1 Cells Exposed to High Glucose and Palmitate |
title_sort | decreased expression and induced nucleocytoplasmic translocation of pancreatic and duodenal homeobox 1 in ins-1 cells exposed to high glucose and palmitate |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3080567/ https://www.ncbi.nlm.nih.gov/pubmed/21537415 http://dx.doi.org/10.4093/dmj.2011.35.1.65 |
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