title: Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases.
abstract: This review resumes the association between mitochondrial function and diseases, especially neurodegenerative diseases. Additionally, it summarizes the major role of IGF-1 as a mitochondrial protector, as studied in several experimental models (cirrhosis, aging …). The contribution of mitochondrial dysfunction to impairments in insulin metabolic signaling is also suggested by gene array analysis showing that reductions in gene expression, that regulates mitochondrial ATP production, are associated with insulin resistance and type 2 diabetes mellitus. Moreover, reductions in oxidative capacity of mitochondrial electron transport chain are manifested in obese, insulin-resistant and diabetic patients. Genetic and environmental factors, oxidative stress, and alterations in mitochondrial biogenesis can adversely affect mitochondrial function, leading to insulin resistance and several pathological conditions, such as type 2 diabetes. Finally, it remains essential to know the exact mechanisms involved in mitochondrial generation and metabolism, mitophagy, apoptosis, and oxidative stress to establish new targets in order to develop potentially effective therapies. One of the newest targets to recover mitochondrial dysfunction could be the administration of IGF-1 at low doses. In the last years, it has been observed that IGF-1 therapy has several beneficial effects: restores physiological IGF-1 levels; improves insulin resistance and lipid metabolism; exerts mitochondrial protection; and has hepatoprotective, neuroprotective, antioxidant and antifibrogenic effects. In consequence, treatment of mitochondrial dysfunctions with low doses of IGF-1 could be a powerful and useful effective therapy to restore normal mitochondrial functions.
authors.affiliation: University CEU-San Pablo, School of Medicine, Department of Physiology, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Sádaba
authors.affiliation: School of Medicine, Tecnologico de Monterrey, Monterrey, Mexico.
authors.forename: I
authors.initials: I
authors.lastname: Martín-Estal
authors.affiliation: University CEU-San Pablo, School of Medicine, Department of Physiology, Institute of Applied Molecular Medicine (IMMA), Madrid, Spain.
authors.forename: J E
authors.initials: JE
authors.lastname: Puche
authors.affiliation: School of Medicine, Tecnologico de Monterrey, Monterrey, Mexico; Fundación de Investigación HM Hospitales, Madrid, Spain. Electronic address: iccortazar@itesm.mx.
authors.forename: I
authors.initials: I
authors.lastname: Castilla-Cortázar
mesh_terms: D000818:Animals; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D007328:Insulin; D020011:Protective Agents; D007334:Insulin-Like Growth Factor I
keywords: Aging; Free radicals; Hepatic cirrhosis; IGF-1; Mitochondria; Mitochondrial diseases; Neurodegenerative diseases; Oxidative stress