title: Insulin resistance is an evolutionarily conserved physiological mechanism at the cellular level for protection against increased oxidative stress.
abstract: Several protective cellular mechanisms protect against the accumulation of reactive oxygen species (ROS) and the concomitant oxidative stress. Therefore, any reduction in glucose or fatty acid flux into cells leading to a decrease in the production of reducing equivalents would also lead to a decreased ROS production and protect cells against oxidative stress. In the presence of insulin, FOXO proteins are localized from the nucleus to the cytoplasm and degraded. An increase in cellular glucose uptake will lead to increased production of ROS. This in turn activates the stress-responsive Jun-N-terminal kinase (JNK), which promotes nuclear translocation of FOXO proteins, upregulating some important target genes including stress resistance. Consequently, insulin resistance should result in decreased cellular ROS production. For this reason, insulin resistance could be a physiological mechanism activated at the cellular level in response to conditions stimulating ROS production and leading to the prevention of oxidative stress, and extension of life. Concerning the whole organism, however, IR is a maladaptive process in the long term causing a diabetic state.
authors.affiliation: Faculty of Medicine, Department of Internal Medicine, Celal Bayar University, Manisa, Turkey. adnan.erol@bayar.edu.tr
authors.forename: Adnan
authors.initials: A
authors.lastname: Erol
mesh_terms: D000818:Animals; D005075:Biological Evolution; D019610:Cytoprotection / Q000502:physiology*; D005947:Glucose / Q000502:physiology; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D000078790:Insulin Secretion; D008928:Mitochondria / Q000187:drug effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000494:pharmacology
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D005947:Glucose