title: Low doses of insulin-like growth factor I improve insulin resistance, lipid metabolism, and oxidative damage in aging rats.
abstract: 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 microg 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.
authors.affiliation: Department of Physiology, School of Medicine, University of Málaga, 29071 Málaga, Spain.
authors.forename: María
authors.initials: M
authors.lastname: García-Fernández
authors.forename: Gloria
authors.initials: G
authors.lastname: Delgado
authors.forename: Juan Enrique
authors.initials: JE
authors.lastname: Puche
authors.forename: Salvador
authors.initials: S
authors.lastname: González-Barón
authors.forename: Inma
authors.initials: I
authors.lastname: Castilla Cortázar
mesh_terms: D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000375:Aging / Q000097:blood / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D007334:Insulin-Like Growth Factor I; D000255:Adenosine Triphosphate; D020782:Matrix Metalloproteinases