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Current Molecular Medicine
ISSN (Print): 1566-5240
ISSN (Online): 1875-5666
VOLUME: 7
ISSUE: 7
DOI: 10.2174/156652407782564408      Price:  $58









Oxidative Stress and the JNK Pathway are Involved in the Development of Type 1 and Type 2 Diabetes

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Author(s): Hideaki Kaneto, Taka-aki Matsuoka, Naoto Katakami, Dan Kawamori, Takeshi Miyatsuka, Kazutomi Yoshiuchi, Tetsuyuki Yasuda, Ken'ya Sakamoto, Yoshimitsu Yamasaki and Munehide Matsuhisa
Pages 674-686 (13)
Abstract:
Failure of pancreatic β-cells is the common characteristic of type 1 and type 2 diabetes. Type 1 diabetes mellitus is induced by destruction of pancreatic β-cells which is mediated by an autoimmune mechanism and consequent inflammatory process. Various inflammatory cytokines and oxidative stress are produced during this process, which has been proposed to play an important role in mediating β-cell destruction. The JNK pathway is also activated by such cytokines and oxidative stress, and is involved in β-cell destruction. Type 2 diabetes is the most prevalent and serious metabolic disease, and β-cell dysfunction and insulin resistance are the hallmark of type 2 diabetes. Under diabetic conditions, chronic hyperglycemia gradually deteriorates β-cell function and aggravates insulin resistance. 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 β-cells dysfunction and insulin resistance. In addition, oxidative stress and activation of the JNK pathway are also 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.
Keywords:
Oxidative stress, the JNK pathway, type 1 diabetes, type 2 diabetes, β-cell glucose toxicity, insulin resistance, atherosclerosis
Affiliation:
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.