title: Targeting mitochondrial alterations to prevent type 2 diabetes--evidence from studies of dietary redox-active compounds.
abstract: As a growing epidemic, type 2 diabetes mellitus (T2DM) has significantly affected the individual's quality of life and economy of the society. Understanding the mechanisms of the disease and discovery of new therapeutic options has become more urgent than ever before. Mitochondrial alterations (e.g. functional alterations, and impaired biogenesis and dynamics) are strongly associated with the development of T2DM. Accumulation of reactive oxygen species or intermediates of incomplete fatty acid oxidation due to mitochondrial deficiency activates stress kinases and dampens insulin signaling. Redox-active compounds such as resveratrol, pyrroloquinoline quinone, and hydroxytyrosol can potently counteract reactive oxygen species, and improve mitochondrial function and biogenesis. Therefore, targeting the mitochondrial alterations with these redox-active compounds may lead to new therapeutic or preventive options for T2DM. In this article, we review the molecular mechanisms of mitochondrial alterations in T2DM, and the action of redox-active compounds to reverse mitochondrial changes and oxidative stress in T2DM. In addition, the current challenges and future directions are discussed and prospected.
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Fralin Translational Obesity Research Center, Virginia Tech Center for Drug Discovery, College of Agriculture and Life Science, Virginia Tech, VA, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Cheng
authors.forename: Eva M
authors.initials: EM
authors.lastname: Schmelz
authors.forename: Dongmin
authors.initials: D
authors.lastname: Liu
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Hulver
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D004032:Diet; D019317:Evidence-Based Medicine; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008954:Models, Biological; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D015398:Signal Transduction
chemical_list: D000975:Antioxidants
keywords: Hydroxytyrosol; Mitochondria; Pyrroloquinoline quinone; Resveratrol; Type 2 diabetes mellitus