1999年8月
Identification of wortmannin-sensitive targets in 3T3-L1 adipocytes - Dissociation of insulin-stimulated glucose uptake and GLUT4 translocation
JOURNAL OF BIOLOGICAL CHEMISTRY
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- 巻
- 274
- 号
- 35
- 開始ページ
- 24677
- 終了ページ
- 24684
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1074/jbc.274.35.24677
- 出版者・発行元
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
The current studies investigated the contribution of phosphatidylinositol 3-kinase (PI3-kinase) isoforms to insulin-stimulated glucose uptake and glucose transporter 4 (GLUT4) translocation, Experiments involving the microinjection of antibodies specific for the p110 catalytic subunit of class I PI3-kinases demonstrated an absolute requirement for this form of the enzyme in GLUT4 translocation. This finding was confirmed by the demonstration that the PI3-kinase antagonist wortmannin inhibits GLUT4 and insulin-responsive aminopeptidase translocation with a dose response identical to that required to inhibit another class I PI3-kinase-dependent event, activation of pp70 SG-kinase, Interestingly, wortmannin inhibited insulin-stimulated glucose uptake at much lower doses, suggesting the existence of a second, higher affinity target of the drug. Subsequent removal of wortmannin from the media shifted this dose-response curve to one resembling that for GLUT4 translocation and pp70 SG-kinase, This is consistent with the lower affinity target being p110, which is irreversibly inhibited by wortmannin, Wortmannin did not reduce glucose uptake in cells stably expressing Myr-Akt, which constitutively induced GLUT4 translocation to the plasma membrane; this demonstrates that wortmannin does not inhibit the transporters directly. In addition to elucidating a second wortmannin-sensitive pathway in 3T3-L1 adipocytes, these studies suggest that the presence of GLUT4 on the plasma membrane is not sufficient for activation of glucose uptake.
- リンク情報
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- DOI
- https://doi.org/10.1074/jbc.274.35.24677
- CiNii Articles
- http://ci.nii.ac.jp/naid/80011263749
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/10455135
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000082193400034&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1074/jbc.274.35.24677
- ISSN : 0021-9258
- CiNii Articles ID : 80011263749
- PubMed ID : 10455135
- Web of Science ID : WOS:000082193400034