| Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. | |
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MedLine Citation:
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PMID: 19780047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Increased plasma levels of free fatty acids (FFA) occur in states of insulin resistance such as obesity and type 2 diabetes mellitus. These high levels of plasma FFA are proposed to play an important role for the development of insulin resistance but the mechanisms involved are still unclear. This study investigated the effects of saturated and unsaturated FFA on insulin sensitivity in parallel with mitochondrial function. C2C12 myotubes were treated for 24 h with 0.1 mM of saturated (palmitic and stearic) and unsaturated (oleic, linoleic, eicosapentaenoic, and docosahexaenoic) FFA. After this period, basal and insulin-stimulated glucose metabolism and mitochondrial function were evaluated. Saturated palmitic and stearic acids decreased insulin-induced glycogen synthesis, glucose oxidation, and lactate production. Basal glucose oxidation was also reduced. Palmitic and stearic acids impaired mitochondrial function as demonstrated by decrease of both mitochondrial hyperpolarization and ATP generation. These FFA also decreased Akt activation by insulin. As opposed to saturated FFA, unsaturated FFA did not impair glucose metabolism and mitochondrial function. Primary cultures of rat skeletal muscle cells exhibited similar responses to saturated FFA as compared to C2C12 cells. These results show that in muscle cells saturated FFA-induced mitochondrial dysfunction associated with impaired insulin-induced glucose metabolism. |
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Authors:
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Sandro M Hirabara; Rui Curi; Pierre Maechler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of cellular physiology Volume: 222 ISSN: 1097-4652 ISO Abbreviation: J. Cell. Physiol. Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2009-11-05 Completed Date: 2009-11-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0050222 Medline TA: J Cell Physiol Country: United States |
Other Details:
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Languages: eng Pagination: 187-94 Citation Subset: IM |
Affiliation:
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Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Butantã, São Paulo, Brazil. sandromh@yahoo.com.br |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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biosynthesis Animals Cell Survival / drug effects Cells, Cultured Fatty Acids / pharmacology* Glucose / metabolism Insulin / pharmacology Insulin Resistance / physiology* Membrane Potential, Mitochondrial / drug effects Mice Mitochondria / drug effects*, enzymology, pathology* Muscle Cells / drug effects*, enzymology, pathology* Muscle Fibers, Skeletal / drug effects, enzymology, pathology Muscle, Skeletal / pathology* Oligomycins / pharmacology Palmitic Acid / pharmacology Phosphorylation / drug effects Proto-Oncogene Proteins c-akt / metabolism Rats Rats, Wistar Stearic Acids / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Oligomycins; 0/Stearic Acids; 11061-68-0/Insulin; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 57-10-3/Palmitic Acid; 57-11-4/stearic acid; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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