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Low Doses of Insulin-Like Growth Factor I Improve Insulin Resistance, Lipid Metabolism, and Oxidative Damage in Aging Rats

Department of Physiology (M.G.-F., G.D., J.E.P., S.G.-B., I.C.C.), School of Medicine, University of Málaga, 29071 Málaga, Spain; and Department of Medical Physiology (J.E.P., I.C.C.), School of Medicine, University CEU-San Pablo, 28668 Madrid, Spain

Address all correspondence and requests for reprints to: Inma Castilla de Cortázar Larrea, M.D., Department of Medical Physiology, School of Medicine, University CEU-San Pablo, Boadilla del Monte, 28668 Madrid, Spain. E-mail: iccortazar{at}uma.es, iccortazar{at}ceu.es.

GH and 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: young healthy controls (17 wk old); untreated old (O) rats (103 wk old); and aging rats (103 wk old) treated with IGF-I during 1 month (2.25 µg IGF-I/100 g body weight^–1·d^–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 O 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. The O group 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.