title: Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic beta-cell dysfunction and insulin resistance.
abstract: 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. Normal beta-cells can compensate for insulin resistance by increasing insulin secretion and/or beta-cell mass, but insufficient compensation leads to the onset of glucose intolerance. Once hyperglycemia becomes apparent, beta-cell function gradually deteriorates and insulin resistance aggravates. Under diabetic conditions, oxidative stress and endoplasmic reticulum stress are induced in various tissues, leading to activation of the c-Jun N-terminal kinase pathway. The activation of c-Jun N-terminal kinase suppresses insulin biosynthesis and interferes with insulin action. Indeed, suppression of c-Jun N-terminal kinase in diabetic mice improves insulin resistance and ameliorates glucose tolerance. Thus, the c-Jun N-terminal kinase pathway plays a central role in pathogenesis of type 2 diabetes and could be a potential target for diabetes therapy.
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.osaka-u.ac.jp
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kaneto
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Dan
authors.initials: D
authors.lastname: Kawamori
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyatsuka
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: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress
chemical_list: D048031:JNK Mitogen-Activated Protein Kinases