Oxidative stress and the JNK pathway in diabetes.
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.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. kaneto@medone.med
Matsuoka
Taka-aki
TA
Nakatani
Yoshihisa
Y
Kawamori
Dan
D
Matsuhisa
Munehide
M
Yamasaki
Yoshimitsu
Y
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
D047428:Protein Kinase Inhibitors; D048670:MAP Kinase Kinase 4