Oxidative stress, ER stress, and the JNK pathway in type 2 diabetes.
Pancreatic beta-cell dysfunction and insulin resistance are observed in type 2 diabetes. Under diabetic conditions, oxidative stress and ER stress are induced in various tissues, leading to activation of the JNK pathway. This JNK activation suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of the JNK pathway in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the JNK pathway plays a central role in pathogenesis of type 2 diabetes and may be a potential target for diabetes therapy.
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.osaka-u.ac.jp
Matsuoka
Taka-Aki
TA
Nakatani
Yoshihisa
Y
Kawamori
Dan
D
Miyatsuka
Takeshi
T
Matsuhisa
Munehide
M
Yamasaki
Yoshimitsu
Y
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007515:Islets of Langerhans / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D051379:Mice; D018384:Oxidative Stress; D015398:Signal Transduction
D048031:JNK Mitogen-Activated Protein Kinases