AJP - Endo Track the topics, authors and articles important to you
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab 296: E157-E164, 2009. First published November 11, 2008; doi:10.1152/ajpendo.90581.2008
0193-1849/09 $8.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
296/1/E157    most recent
90581.2008v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ikubo, M.
Right arrow Articles by Sasaoka, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ikubo, M.
Right arrow Articles by Sasaoka, T.

Impact of lipid phosphatases SHIP2 and PTEN on the time- and Akt-isoform-specific amelioration of TNF-{alpha}-induced insulin resistance in 3T3-L1 adipocytes

Mariko Ikubo,1 Tsutomu Wada,2 Kazuhito Fukui,1 Manabu Ishiki,1 Hajime Ishihara,3 Tomoichiro Asano,4 Hiroshi Tsuneki,2 and Toshiyasu Sasaoka2

1Department of Internal Medicine and 2Department of Clinical Pharmacology, University of Toyama; 3Sainou South Hospital, Toyama; and 4Division of Molecular Medical Science, Hiroshima University, Hiroshima, Japan

Submitted 10 July 2008 ; accepted in final form 4 November 2008

TNF-{alpha} is a major contributor to the pathogenesis of insulin resistance associated with obesity and inflammation by serine phosphorylating and degrading insulin receptor substrate-1. Presently, we further found that pretreatment with TNF-{alpha} inhibited insulin-induced phosphorylation of Akt2 greater than Akt1. Since lipid phosphatases SH2-containing inositol 5'-phoshatase 2 (SHIP2) and phosphatase and tensin homologs deleted on chromosome 10 (PTEN) are negative regulators of insulin's metabolic signaling at the step downstream of phosphatidylinositol 3-kinase, we investigated the Akt isoform-specific properties of these phosphatases in the negative regulation after short- and long-term insulin treatment and examined the influence of inhibition on the amelioration of insulin resistance caused by TNF-{alpha} in 3T3-L1 adipocytes. Adenovirus-mediated overexpression of WT-SHIP2 decreased the phosphorylation of Akt2 greater than Akt1 after insulin stimulation up to 15 min. Expression of a dominant-negative {Delta}IP-SHIP2 enhanced the phosphorylation of Akt2 up to 120 min. On the other hand, overexpression of WT-PTEN inhibited the phosphorylation of both Akt1 and Akt2 after short- but not long-term insulin treatment. The expression of {Delta}IP-PTEN enhanced the phosphorylation of Akt1 at 120 min and that of Akt2 at 2 min. Interestingly, the expression of {Delta}IP-SHIP2, but not {Delta}IP-PTEN, protected against the TNF-{alpha} inhibition of insulin-induced phosphorylation of Akt2, GSK3, and AS160, whereas both improved the TNF-{alpha} inhibition of insulin-induced 2-deoxyglucose uptake. The results indicate that these lipid phosphatases possess different characteristics according to the time and preference of Akt isoform-dependent signaling in the negative regulation of the metabolic actions of insulin, whereas both inhibitions are effective in the amelioration of insulin resistance caused by TNF-{alpha}.

insulin signaling; SH2-containing inositol 5'-phoshatase 2; phosphatase and tensin homologs deleted on chromosome 10


Address for reprint requests and other correspondence: T. Sasaoka, Dept. of Clinical Pharmacology, Univ. of Toyama, 2630 Sugitani, Toyama 930-0194, Japan (e-mail: tsasaoka{at}pha.u-toyama.ac.jp)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2009 by the American Physiological Society.