title: Oxidative stress and the JNK pathway in diabetes.
abstract: Under diabetic conditions, oxidative stress is induced and the JNK pathway is activated, which is involved in deterioration of pancreatic beta-cell function found in diabetes. Oxidative stress and/or activation of the JNK pathway suppress insulin gene expression, accompanied by reduction of PDX-1 DNA binding activity. Treatment with antioxidants and/or suppression of the JNK pathway protect beta-cells from some of the toxic effects of hyperglycemia. The JNK pathway is also involved in the progression of insulin resistance; suppression of the JNK pathway in obese diabetic mice markedly improves insulin resistance and ameliorates glucose tolerance. The phosphorylation state of key molecules for insulin signaling is altered upon modification of the JNK pathway. Taken together, the JNK pathway plays a crucial role in progression of insulin resistance as well as beta-cell dysfunction found in diabetes and thus could be a potential therapeutic target for diabetes.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Taka-aki
authors.initials: TA
authors.lastname: Matsuoka
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.forename: Munehide
authors.initials: M
authors.lastname: Matsuhisa
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamasaki
mesh_terms: D017209:Apoptosis; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D050417:Insulin-Secreting Cells / Q000502:physiology; D007515:Islets of Langerhans / Q000503:physiopathology; D048670:MAP Kinase Kinase 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D048670:MAP Kinase Kinase 4