| Chronic treatment with epoxyeicosatrienoic acids modulates insulin signaling and prevents insulin resistance in hepatocytes. | |
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MedLine Citation:
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PMID: 21040800 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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Epoxyeicosatrienoic acids (EETs) are arachidonic acid metabolites produced by cytochrome P450 epoxygenases which are highly expressed in hepatocytes. The functions of EETs in hepatocytes are not well understood. In this study, we investigated the effects of 14,15-EETs treatment on the insulin signal transduction pathway in hepatocytes. We report that chronic treatment, not acute treatment, with 30μM 14,15-EETs prevents palmitate induced insulin resistance and potentiates insulin action in cultured HepG2 hepatocytes. 14,15-EETs increase Akt phosphorylation at S473, activating Akt, in an insulin dependent manner in HepG2 cells. Under insulin resistant conditions induced by palmitate, 14,15-EETs restore the insulin response by increasing S473-phosphorylated Akt. 8,9-EETs and 11,12-EETs demonstrated similar effects to 14,15-EETs. Furthermore, 14,15-EETs potentiate insulin-suppression of gluconeogenesis in cultured H4IIE hepatocytes. To elucidate the mechanism of EETs function, we analyzed the insulin signaling factors upstream of Akt. Inhibition of phosphatidylinositol 3-kinase (PI3K) with LY294002 attenuated the 14,15-EETs-induced activating phosphorylation of Akt. 14,15-EETs reduced palmitate-stimulated phosphorylation of IRS-1 on S312 and phosphorylation of c-Jun N-terminal kinase (JNK) at threonine 183 and tyrosine 185 residues. The regulation of insulin sensitivity in cultured hepatocytes by chronic 14,15-EETs treatment appears to involve the JNK-IRS-PI3K pathway. The requirement of chronic treatment with EETs suggests that the effects of EETs on insulin response may be indirect. |
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Authors:
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Jill E Skepner; Lorraine D Shelly; Chengjie Ji; Benjamin Reidich; Yi Luo |
Publication Detail:
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Type: Journal Article Date: 2010-10-30 |
Journal Detail:
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Title: Prostaglandins & other lipid mediators Volume: 94 ISSN: 1098-8823 ISO Abbreviation: Prostaglandins Other Lipid Mediat. Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-02-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9808648 Medline TA: Prostaglandins Other Lipid Mediat Country: United States |
Other Details:
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Languages: eng Pagination: 3-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Cardiovascular and Metabolic Diseases, Pfizer Global Research Division, Pfizer Inc., Groton, CT 06340, United States. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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