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This version published online on January 10, 2008
Endocrinology, doi:10.1210/en.2007-1190
A more recent version of this article appeared on May 1, 2008
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*Seniors' Health

Submitted on August 28, 2007
Accepted on January 3, 2008

Low Doses of Insulin-Like Growth Factor I improve insulin resistance, lipid metabolism, and oxidative damage in Aging Rats

María García-Fernández, Gloria Delgado, Juan Enrique Puche, Salvador González-Barón, and Inma Castilla de Cortázar*

Department of Physiology, School of Medicine, University of Málaga, Málaga, Spain; Department of Medical Physiology, School of Medicine, University CEU-USP, Madrid, Spain

* To whom correspondence should be addressed. E-mail: iccortazar{at}uma.es or iccortazar@ceu.es.

Growth Hormone (GH) and Insulin-like Growth Factor I (IGF-I) concentrations decline with age. Age-related changes appear to be linked to decreases in the anabolic hormones, GH and IGF-I.

The aim of this study was to investigate the antioxidant, anabolic and metabolic effects of the IGF-I replacement therapy, at low doses, in aging rats. Three experimental groups were included in this protocol: yCO, young healthy controls (17 week old); O, untreated old rats (103 week old); and O+IGF-I, aging rats (103 week old) treated with IGF-I during 1 month (2.25µg IGF-I ·100 g body weight-1 ·day-1).

Compared with young controls, untreated aging rats showed a reduction of IGF-I and testosterone levels and a decrease of serum total antioxidant status, which were corrected by IGF-I therapy. In addition, untreated old rats presented increased levels of serum glucose with hyperinsulinemia, cholesterol and triglycerides and a reduction of free fatty acid concentrations. IGF-I therapy was able to revert insulin resistance and to reduce cholesterol and triglycerides levels increasing significantly free fatty acid concentrations.

Old rats showed higher oxidative damage in brain and liver tissues associated with alterations in antioxidant enzyme activities. IGF-I therapy reduced oxidative damage in brain and liver, normalizing antioxidant enzyme activities and mitochondrial dysfunction.

In conclusion, low doses of IGF-I restore circulating IGF-I, improve glucose and lipid metabolism, increase testosterone levels and serum total antioxidant capability and reduce oxidative damage in brain and liver associated with a normalization of antioxidant enzyme activities and mitochondrial function.


Key words: Aging • IGF-I • oxidative damage • antioxidant enzymes • neuroprotection • hepatoprotection • mitochondrial dysfunction • insulin resistance







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