Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases

• Published in: Biochimica et biophysica acta 2016-07, Vol.1862 (7), p.1267-1278
• Main Authors: Sádaba, M.C., Martín-Estal, I., Puche, J.E., Castilla-Cortázar, I.
• Format: Article
• Language: English
• Subjects: Aging; Animals; Free radicals; Hepatic cirrhosis; Humans; IGF-1; Insulin - metabolism; Insulin Resistance; Insulin-Like Growth Factor I - administration & dosage; Insulin-Like Growth Factor I - therapeutic use; Mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondria - pathology; Mitochondrial diseases; Mitochondrial Diseases - drug therapy; Mitochondrial Diseases - metabolism; Mitochondrial Diseases - pathology; Neurodegenerative diseases; Oxidative stress; Oxidative Stress - drug effects; Protective Agents - administration & dosage; Protective Agents - therapeutic use
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2016.03.010

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. •Mitochondrial dysfunction has been shown to compromise insulin signaling and oxidative capacity of mitochondrial electron transport chain.•In neurodegenerative diseases, it has been found a mitochondrial dysfunction, leading to an increase in oxidative stress.•The mere partial IGF-1 deficiency in animals is shown to produce mitochondrial dysfunction.•The administration of low doses of IGF-1 has beneficial effects: restores physiological IGF-1 levels and improves insulin resistance.•The administration of low doses of IGF-1 has hepatoprotective, neuroprotective and antioxidant effects and exherts mitocondrial protection.