| Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes. | |
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MedLine Citation:
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PMID: 21636835 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Both insulin and the cell death-inducing DNA fragmentation factor-α-like effector (CIDE) family play important roles in apoptosis and lipid droplet formation. Previously, we reported that CIDEA and CIDEC are differentially regulated by insulin and contribute separately to insulin-induced anti-apoptosis and lipid droplet formation in human adipocytes. However, the upstream signals of CIDE proteins remain unclear. Here, we investigated the signaling molecules involved in insulin regulation of CIDEA and CIDEC expression. The phosphatidylinositol 3-kinase (PI3K) inhibitors wortmannin and PI-103 blocked both insulin-induced downregulation of CIDEA and upregulation of CIDEC. The Akt inhibitor API-2 and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 selectively inhibited insulin regulation of CIDEA and CIDEC expression, respectively, whereas the MAPK/ERK kinase inhibitor U0126 and the p38 inhibitor SB203580 did not. Small interfering RNA-mediated depletion of Akt1/2 prevented insulin-induced downregulation of CIDEA and inhibition of apoptosis. Depletion of JNK2, but not JNK1, inhibited insulin-induced upregulation of CIDEC and lipid droplet enlargement. Furthermore, insulin increased both Akt and JNK phosphorylation, which was abrogated by the PI3K inhibitors. These results suggest that insulin regulates CIDEA and CIDEC expression via PI3K, and it regulates expression of each protein via Akt1/2- and JNK2-dependent pathways, respectively, in human adipocytes. |
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Authors:
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Minoru Ito; Michiaki Nagasawa; Naoki Omae; Tomohiro Ide; Yunike Akasaka; Koji Murakami |
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Publication Detail:
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Type: Journal Article Date: 2011-06-02 |
Journal Detail:
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Title: Journal of lipid research Volume: 52 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-07-18 Completed Date: 2011-11-08 Revised Date: 2012-09-25 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1450-60 Citation Subset: IM |
Affiliation:
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Discovery Research Laboratories, Kyorin Pharmaceutical Co. Ltd., Tochigi 329-0114, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adipocytes
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cytology,
metabolism* Apoptosis / drug effects Apoptosis Regulatory Proteins / genetics, metabolism* Chlorpropamide / analogs & derivatives, pharmacology DNA Fragmentation / drug effects Down-Regulation Female Furans / pharmacology Gene Expression Regulation* Gene Silencing / drug effects Humans Insulin* / metabolism, pharmacology Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors, genetics, metabolism Obesity / genetics, metabolism*, pathology, physiopathology Phosphatidylinositol 3-Kinases / antagonists & inhibitors, genetics, metabolism Phosphorylation / drug effects Protein Kinase Inhibitors / pharmacology Proteins / genetics, metabolism* Proto-Oncogene Proteins c-akt / antagonists & inhibitors, genetics, metabolism Pyridines / pharmacology Pyrimidines / pharmacology RNA, Small Interfering / pharmacology Signal Transduction* Up-Regulation |
| Chemical | |
Reg. No./Substance:
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0/API 2; 0/Apoptosis Regulatory Proteins; 0/CIDEA protein, human; 0/CIDEC protein, human; 0/Furans; 0/Insulin; 0/PI103; 0/Protein Kinase Inhibitors; 0/Proteins; 0/Pyridines; 0/Pyrimidines; 0/RNA, Small Interfering; 94-20-2/Chlorpropamide; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.1.24/Mitogen-Activated Protein Kinase 9; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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