Involvement of oxidative stress in the pathogenesis of diabetes.
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.
Kaneto
Hideaki
H
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan. kaneto@medone.med.osaka-u.ac.jp
Katakami
Naoto
N
Kawamori
Dan
D
Miyatsuka
Takeshi
T
Sakamoto
Ken'ya
K
Matsuoka
Taka-Aki
TA
Matsuhisa
Munehide
M
Yamasaki
Yoshimitsu
Y
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
D048670:MAP Kinase Kinase 4