Journals of Gerontology Series A: Biological Sciences and Medical Sciences Large Type Edition
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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 60:28-34 (2005)
© 2005 The Gerontological Society of America

Effects of Long-Term Caloric Restriction on Early Steps of the Insulin-Signaling System in Mouse Skeletal Muscle

Danila P. Argentino1, Fernando P. Dominici1, Khalid Al-Regaiey2, Michael S. Bonkowski2, Andrzej Bartke2 and Daniel Turyn1,

1 Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
2 Departments of Physiology, Medicine, and Pharmacology, School of Medicine, Southern Illinois University, Springfield.

Address correspondence to Daniel Turyn, Instituto de Química y Fisicoquímica Biológicas (IQUIFIB), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junin 956 (1113), Buenos Aires, Argentina. E-mail: dturyn{at}qb.ffyb.uba.ar

In this study, we analyzed the effects of long-term (14 months) caloric restriction (CR) on the first steps of the insulin signaling system in skeletal muscle of normal mice. CR induced a significant decrease in serum insulin and glucose levels, indicating an enhancement of insulin sensitivity. CR reduced the in vivo insulin-induced phosphorylation of the insulin receptor substrate (IRS)-1 by 27%, but this difference was not significant (p =.298). CR reduced insulin receptor (IR) abundance by 34% from the ad libitum values, but this difference did not reach significance (p =.246). The abundance of the p85 regulatory subunit of PI3K and glucose transporter 4 was unaltered after CR. However, IRS-1 abundance was significantly increased by 42% in muscle of mice exposed to CR. These findings indicate that the CR-induced improvement of insulin action in mice is not related to changes in glucose transporter 4, the p85 regulatory subunit of PI3K, or IR abundance in skeletal muscle but might be related to an increase in IRS-1 abundance in this tissue.




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