Cargando…
Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver
Dexamethasone is a glucocorticoid analog, which is reported to induce insulin resistance and to exacerbate diabetic symptoms. In this study, we investigated the association between mitochondrial dysfunction and the pathophysiology of dexamethasone-induced insulin resistance. An insulin resistance mo...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572075/ https://www.ncbi.nlm.nih.gov/pubmed/31126054 http://dx.doi.org/10.3390/molecules24101982 |
_version_ | 1783427557492785152 |
---|---|
author | Luan, Guangxiang Li, Gang Ma, Xiao Jin, Youcai Hu, Na Li, Ji Wang, Zhenhua Wang, Honglun |
author_facet | Luan, Guangxiang Li, Gang Ma, Xiao Jin, Youcai Hu, Na Li, Ji Wang, Zhenhua Wang, Honglun |
author_sort | Luan, Guangxiang |
collection | PubMed |
description | Dexamethasone is a glucocorticoid analog, which is reported to induce insulin resistance and to exacerbate diabetic symptoms. In this study, we investigated the association between mitochondrial dysfunction and the pathophysiology of dexamethasone-induced insulin resistance. An insulin resistance model in 3T3-L1 adipocyte was established by 48-h treatment of 1 μM dexamethasone, followed with the detection of mitochondrial function. Results showed that dexamethasone impaired insulin-induced glucose uptake and caused mitochondrial dysfunction. Abnormality in mitochondrial function was supported by decreased intracellular ATP and mitochondrial membrane potential (MMP), increased intracellular and mitochondrial reactive oxygen species (ROS) and mtDNA damage. Mitochondrial dynamic changes and biogenesis were suggested by decreased Drp1, increased Mfn2, and decreased PGC-1, NRF1, and TFam, respectively. The mitochondrial DNA (mtDNA) copy number exhibited no change while the mitochondrial mass increased. In agreement, studies in isolated mitochondria from mouse liver also showed dexamethasone-induced reduction of mitochondrial respiratory function, as suggested by decreased mitochondrial respiration controlling rate (RCR), lower MMP, declined ATP synthesis, opening of the mitochondrial permeability transition pore (mPTP), damage of mtDNA, and the accumulation of ROS. In summary, our study suggests that mitochondrial dysfunction occurs along with dexamethasone-induced insulin resistance in 3T3 L1 adipocytes and might be a potential mechanism of dexamethasone-induced insulin resistance. |
format | Online Article Text |
id | pubmed-6572075 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65720752019-06-18 Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver Luan, Guangxiang Li, Gang Ma, Xiao Jin, Youcai Hu, Na Li, Ji Wang, Zhenhua Wang, Honglun Molecules Article Dexamethasone is a glucocorticoid analog, which is reported to induce insulin resistance and to exacerbate diabetic symptoms. In this study, we investigated the association between mitochondrial dysfunction and the pathophysiology of dexamethasone-induced insulin resistance. An insulin resistance model in 3T3-L1 adipocyte was established by 48-h treatment of 1 μM dexamethasone, followed with the detection of mitochondrial function. Results showed that dexamethasone impaired insulin-induced glucose uptake and caused mitochondrial dysfunction. Abnormality in mitochondrial function was supported by decreased intracellular ATP and mitochondrial membrane potential (MMP), increased intracellular and mitochondrial reactive oxygen species (ROS) and mtDNA damage. Mitochondrial dynamic changes and biogenesis were suggested by decreased Drp1, increased Mfn2, and decreased PGC-1, NRF1, and TFam, respectively. The mitochondrial DNA (mtDNA) copy number exhibited no change while the mitochondrial mass increased. In agreement, studies in isolated mitochondria from mouse liver also showed dexamethasone-induced reduction of mitochondrial respiratory function, as suggested by decreased mitochondrial respiration controlling rate (RCR), lower MMP, declined ATP synthesis, opening of the mitochondrial permeability transition pore (mPTP), damage of mtDNA, and the accumulation of ROS. In summary, our study suggests that mitochondrial dysfunction occurs along with dexamethasone-induced insulin resistance in 3T3 L1 adipocytes and might be a potential mechanism of dexamethasone-induced insulin resistance. MDPI 2019-05-23 /pmc/articles/PMC6572075/ /pubmed/31126054 http://dx.doi.org/10.3390/molecules24101982 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Luan, Guangxiang Li, Gang Ma, Xiao Jin, Youcai Hu, Na Li, Ji Wang, Zhenhua Wang, Honglun Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title | Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title_full | Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title_fullStr | Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title_full_unstemmed | Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title_short | Dexamethasone-Induced Mitochondrial Dysfunction and Insulin Resistance-Study in 3T3-L1 Adipocytes and Mitochondria Isolated from Mouse Liver |
title_sort | dexamethasone-induced mitochondrial dysfunction and insulin resistance-study in 3t3-l1 adipocytes and mitochondria isolated from mouse liver |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6572075/ https://www.ncbi.nlm.nih.gov/pubmed/31126054 http://dx.doi.org/10.3390/molecules24101982 |
work_keys_str_mv | AT luanguangxiang dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT ligang dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT maxiao dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT jinyoucai dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT huna dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT liji dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT wangzhenhua dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver AT wanghonglun dexamethasoneinducedmitochondrialdysfunctionandinsulinresistancestudyin3t3l1adipocytesandmitochondriaisolatedfrommouseliver |