| Mitochondrial dysfunction is induced by high levels of glucose and free fatty acids in 3T3-L1 adipocytes. | |
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MedLine Citation:
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PMID: 20144685 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hyperglycemia and high free fatty acids (FFAs) are two well-known characteristics of type 2 diabetes, and are also implicated in the etiology of insulin resistance. However, their roles in mitochondrial dysfunction of white adipocytes are not well-studied. In this study, we investigated the effects of high glucose (25 mM), high free fatty acids (FFAs, 1mM), or a combination of both high glucose+high FFAs on mitochondrial function in differentiated 3T3-L1 adipocytes after 48 h of treatment. We found that high glucose, high FFAs, or high glucose+high FFAs reduced insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In addition, the mitochondria became smaller and more compact. Levels of the mitofusion protein mfn1 decreased and levels of the mitofission protein Drp1 increased as compared to controls. NRF1 was downregulated, and PGC-1 beta levels were diminished in the high glucose and high glucose+high FFAs conditions. Levels of PGC-1 alpha and mtTFA mRNA were greatly downregulated. No difference was found in the mitochondrial DNA (mtDNA) and intracellular ATP levels of treated cells compared to control cells. Cells treated with high glucose or high FFAs accumulated significant amounts of reactive oxygen species (ROS) and displayed a loss of the mitochondrial membrane potential. High glucose and high glucose+high FFAs led to similar decreases in intramitochondrial calcium concentration, although high FFAs had no effect. Therefore, high glucose and high FFAs can regulate insulin sensitivity, and mitochondrial dysfunction may occur in this process. |
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Authors:
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Chun-Lin Gao; Chun Zhu; Ya-Ping Zhao; Xiao-Hui Chen; Chen-Bo Ji; Chun-Mei Zhang; Jin-Gai Zhu; Zheng-Kun Xia; Mei-Ling Tong; Xi-Rong Guo |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-06 |
Journal Detail:
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Title: Molecular and cellular endocrinology Volume: 320 ISSN: 1872-8057 ISO Abbreviation: Mol. Cell. Endocrinol. Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-03-23 Completed Date: 2010-06-08 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7500844 Medline TA: Mol Cell Endocrinol Country: Ireland |
Other Details:
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Languages: eng Pagination: 25-33 Citation Subset: IM |
Copyright Information:
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(c) 2010 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Department of Pediatrics, Nanjing Maternal and Child Health Hospital of Nanjing Medical University, Nanjing 210004, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Adenosine Triphosphate / metabolism Adipocytes / cytology, drug effects*, metabolism*, ultrastructure Animals Calcium / metabolism DNA, Mitochondrial / metabolism Fatty Acids, Nonesterified / pharmacology* Glucose / pharmacology* Insulin / pharmacology Intracellular Space / drug effects, metabolism Membrane Potential, Mitochondrial / drug effects Mice Mitochondria / drug effects*, metabolism*, ultrastructure Reactive Oxygen Species / metabolism |
| Chemical | |
Reg. No./Substance:
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0/DNA, Mitochondrial; 0/Fatty Acids, Nonesterified; 0/Reactive Oxygen Species; 11061-68-0/Insulin; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium |
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