Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
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
Google Scholar
Right arrow Articles by Giani, J. F.
Right arrow Articles by Dominici, F. P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Giani, J. F.
Right arrow Articles by Dominici, F. P.
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:788-797 (2008)
© 2008 The Gerontological Society of America

Insulin Signaling Cascade in the Hearts of Long-Lived Growth Hormone Receptor Knockout Mice: Effects of Calorie Restriction

Jorge F. Giani, Michael S. Bonkowski, Marina C. Muñoz, Michal M. Masternak, Daniel Turyn, Andrzej Bartke and Fernando P. Dominici

1 Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
2 Geriatrics Research, Departments of Internal Medicine and Physiology, and 3 Department of Pharmacology, School of Medicine, Southern Illinois University, Springfield.

Address correspondence to Fernando Pablo Dominici, PhD, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Junin 956, sexto piso, Buenos Aires, Buenos Aires 1113, Argentina. E-mail: dominici{at}qb.ffyb.uba.ar

Calorie restriction (CR) improves insulin sensitivity and increases life span in normal but not in long-lived growth hormone-resistant knockout (GHRKO) mice. In this study, we examined interactive effects of GH resistance and long-term CR on cardiac insulin action. GHRKO mice exhibited marked increases in the insulin-induced phosphorylation of the insulin receptor (IR), insulin receptor substrate-1 (IRS-1), Akt, and ERK1/2 along with elevated insulin-stimulated IRS-1-associated regulatory subunit of phosphatidylinositol 3-kinase in the heart. These changes were associated with elevated protein levels of IR, IRS-1, and Akt and with a down-regulation of cardiac glucose transporter 4 (GLUT4). In normal mice, CR induced an important increase in the phosphorylation of cardiac Akt without elevation of Akt protein, reaching activation levels similar to those seen in GHRKO mice. This change may be cardioprotective and thus contribute to increased longevity in response to CR. Interestingly, the insulin signaling cascade in the heart of GHRKO mice was unaffected by CR.

Key Words: GHRKO mice • Calorie restriction • Heart • Insulin signaling






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
All GSA journals The Gerontologist
Journals of Gerontology Series B: Psychological Sciences and Social Sciences
Copyright © 2008 by The Gerontological Society of America.