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Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation
Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whet...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800673/ https://www.ncbi.nlm.nih.gov/pubmed/26997114 http://dx.doi.org/10.1038/srep23403 |
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author | Chang, Tien-Jyun Tseng, Hsing-Chi Liu, Meng-Wei Chang, Yi-Cheng Hsieh, Meng-Lun Chuang, Lee-Ming |
author_facet | Chang, Tien-Jyun Tseng, Hsing-Chi Liu, Meng-Wei Chang, Yi-Cheng Hsieh, Meng-Lun Chuang, Lee-Ming |
author_sort | Chang, Tien-Jyun |
collection | PubMed |
description | Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whether metformin prevents MG-induced beta cell apoptosis is controversial. Here, we explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. MG treatment induced apoptosis of beta cells, impaired mitochondrial function, and prolonged activation of AMP-dependent protein kinase (AMPK). The MG-induced pro-apoptotic effects were abolished by an AMPK inhibitor. Pretreatment of GLP-1 reversed MG-induced apoptosis, and mitochondrial dysfunction, and suppressed prolonged AMPK activation. Pretreatment of GLP-1 reversed AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR)-induced apoptosis, and suppressed prolonged AMPK activation. However, metformin neither leads to beta cell apoptosis nor ameliorates MG-induced beta cell apoptosis. In parallel, GLP-1 also prevents MG-induced beta cell apoptosis through PKA and PI3K-dependent pathway. In conclusion, these data indicates GLP-1 but not metformin protects MG-induced beta cell apoptosis through improving mitochondrial function, and alleviating the prolonged AMPK activation. Whether adding GLP-1 to metformin provides better beta cell survival and delays disease progression remains to be validated. |
format | Online Article Text |
id | pubmed-4800673 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48006732016-03-22 Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation Chang, Tien-Jyun Tseng, Hsing-Chi Liu, Meng-Wei Chang, Yi-Cheng Hsieh, Meng-Lun Chuang, Lee-Ming Sci Rep Article Accumulation of methylglyoxal (MG) contributes to glucotoxicity and mediates beta cell apoptosis. The molecular mechanism by which GLP-1 protects MG-induced beta cell apoptosis remains unclear. Metformin is a first-line drug for treating type 2 diabetes associated with AMPK activation. However, whether metformin prevents MG-induced beta cell apoptosis is controversial. Here, we explored the signaling pathway involved in the anti-apoptotic effect of GLP-1, and investigated whether metformin had an anti-apoptotic effect on beta cells. MG treatment induced apoptosis of beta cells, impaired mitochondrial function, and prolonged activation of AMP-dependent protein kinase (AMPK). The MG-induced pro-apoptotic effects were abolished by an AMPK inhibitor. Pretreatment of GLP-1 reversed MG-induced apoptosis, and mitochondrial dysfunction, and suppressed prolonged AMPK activation. Pretreatment of GLP-1 reversed AMPK activator 5-aminoimidazole-4-carboxamide riboside (AICAR)-induced apoptosis, and suppressed prolonged AMPK activation. However, metformin neither leads to beta cell apoptosis nor ameliorates MG-induced beta cell apoptosis. In parallel, GLP-1 also prevents MG-induced beta cell apoptosis through PKA and PI3K-dependent pathway. In conclusion, these data indicates GLP-1 but not metformin protects MG-induced beta cell apoptosis through improving mitochondrial function, and alleviating the prolonged AMPK activation. Whether adding GLP-1 to metformin provides better beta cell survival and delays disease progression remains to be validated. Nature Publishing Group 2016-03-21 /pmc/articles/PMC4800673/ /pubmed/26997114 http://dx.doi.org/10.1038/srep23403 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Chang, Tien-Jyun Tseng, Hsing-Chi Liu, Meng-Wei Chang, Yi-Cheng Hsieh, Meng-Lun Chuang, Lee-Ming Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title_full | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title_fullStr | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title_full_unstemmed | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title_short | Glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged AMPK activation |
title_sort | glucagon-like peptide-1 prevents methylglyoxal-induced apoptosis of beta cells through improving mitochondrial function and suppressing prolonged ampk activation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800673/ https://www.ncbi.nlm.nih.gov/pubmed/26997114 http://dx.doi.org/10.1038/srep23403 |
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