title: Involvement of oxidative stress in the pathogenesis of diabetes.
abstract: Pancreatic beta-cell failure is the common characteristic of type 1 and type 2 diabetes. Type 1 diabetes is induced by pancreatic beta-cell destruction, which is mediated by an autoimmune mechanism and consequent inflammatory process. Various inflammatory cytokines and oxidative stress produced by islet-infiltrating immune cells have been proposed to play an important role in mediating the destruction of beta cells. The JNK pathway is also activated by such cytokines and oxidative stress and is involved in beta-cell destruction. Type 2 diabetes is the most prevalent and serious metabolic disease affecting people all over the world. Pancreatic beta-cell dysfunction and insulin resistance are the hallmark of type 2 diabetes. Once hyperglycemia becomes apparent, beta-cell function gradually deteriorates, and insulin resistance is aggravated. This process is called "glucose toxicity." Under such conditions, oxidative stress is provoked, and the JNK pathway is activated, which is likely involved in pancreatic beta-cell dysfunction and insulin resistance. In addition, oxidative stress and activation of the JNK pathway are involved in the progression of atherosclerosis, which is often observed under diabetic conditions. Taken together, it is likely that oxidative stress and subsequent activation of the JNK pathway are involved in the pathogenesis of type 1 and type 2 diabetes.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. kaneto@medone.med.osaka-u.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Naoto
authors.initials: N
authors.lastname: Katakami
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
authors.forename: Ken'ya
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000473:pathology / Q000503:physiopathology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D018384:Oxidative Stress
chemical_list: D048670:MAP Kinase Kinase 4