help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

Endocrinology, doi:10.1210/en.2008-0439
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
149/8/3900    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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
Right arrow Request Copyright Permission
Google Scholar
Right arrow Articles by Schakman, O.
Right arrow Articles by Thissen, J. P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schakman, O.
Right arrow Articles by Thissen, J. P.
Endocrinology Vol. 149, No. 8 3900-3908
Copyright © 2008 by The Endocrine Society

Role of Akt/GSK-3β/β-Catenin Transduction Pathway in the Muscle Anti-Atrophy Action of Insulin-Like Growth Factor-I in Glucocorticoid-Treated Rats

O. Schakman, S. Kalista, L. Bertrand, P. Lause, J. Verniers, J. M. Ketelslegers and J. P. Thissen

Université Catholique de Louvain, School of Medicine, Diabetes & Nutrition Unit (O.S., S.K., P.L., J.V., J.M.K., J.P.T.), and Cardiology Unit (L.B.), B-1200 Bruxelles, Belgium

Address all correspondence and requests for reprints to: Olivier Schakman, Unité de Diabétologie et Nutrition, Université Catholique de Louvain, 54 avenue Hippocrate, B-1200 Brussels, Belgium. E-mail: olivier.schakman{at}uclouvain.be.

Decrease of muscle IGF-I plays a critical role in muscle atrophy caused by glucocorticoids (GCs) because IGF-I gene electrotransfer prevents muscle atrophy caused by GCs. The goal of the present study was to identify the intracellular mediators responsible for the IGF-I anti-atrophic action in GC-induced muscle atrophy. We first assessed the IGF-I transduction pathway alterations caused by GC administration and their reversibility by local IGF-I overexpression performed by electrotransfer. Muscle atrophy induced by dexamethasone (dexa) administration occurred with a decrease in Akt (–53%; P <0.01) phosphorylation together with a decrease in β-catenin protein levels (–40%; P <0.001). Prevention of atrophy by IGF-I was associated with restoration of Akt phosphorylation and β-catenin levels. We then investigated whether muscle overexpression of these intracellular mediators could mimic the IGF-I anti-atrophic effects. Overexpression of a constitutively active form of Akt induced a marked fiber hypertrophy in dexa-treated animals (+175% of cross-sectional area; P <0.001) and prevented dexa-induced atrophy. This hypertrophy was associated with an increase in phosphorylated GSK-3β (+17%; P <0.05) and in β-catenin content (+35%; P <0.05). Furthermore, overexpression of a dominant-negative GSK-3β or a stable form of β-catenin increased fiber cross-sectional area by, respectively, 23% (P <0.001) and 29% (P <0.001) in dexa-treated rats, preventing completely the atrophic effect of GC. In conclusion, this work indicates that Akt, GSK-3β, and β-catenin probably contribute together to the IGF-I anti-atrophic effect in GC-induced muscle atrophy.







HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2008 by The Endocrine Society