Kaneto Hideaki, Matsuoka Taka-aki, Katakami Naoto, Kawamori Dan, Miyatsuka Takeshi, Yoshiuchi Kazutomi, Yasuda Tetsuyuki, Sakamoto Ken'ya, Yamasaki Yoshimitsu, Matsuhisa Munehide
Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Curr Mol Med. 2007 Nov;7(7):674-86. doi: 10.2174/156652407782564408.
Failure of pancreatic beta-cells is the common characteristic of type 1 and type 2 diabetes. Type 1 diabetes mellitus is induced by destruction of pancreatic beta-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 beta-cell destruction. 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, and beta-cell dysfunction and insulin resistance are the hallmark of type 2 diabetes. Under diabetic conditions, chronic hyperglycemia gradually deteriorates beta-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 beta-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.
胰腺β细胞功能衰竭是1型和2型糖尿病的共同特征。1型糖尿病是由胰腺β细胞破坏所致，这种破坏由自身免疫机制及随之而来的炎症过程介导。在此过程中会产生多种炎性细胞因子和氧化应激，有人认为它们在介导β细胞破坏中起重要作用。JNK通路也会被此类细胞因子和氧化应激激活，并参与β细胞破坏过程。2型糖尿病是最常见且严重的代谢性疾病，β细胞功能障碍和胰岛素抵抗是2型糖尿病的标志。在糖尿病状态下，慢性高血糖会逐渐损害β细胞功能并加重胰岛素抵抗。这个过程被称为“葡萄糖毒性”。在这种情况下，会引发氧化应激并激活JNK通路，这可能与胰腺β细胞功能障碍和胰岛素抵抗有关。此外，氧化应激和JNK通路的激活也参与了糖尿病状态下常见的动脉粥样硬化的进展。综上所述，氧化应激及随后JNK通路的激活可能参与了1型和2型糖尿病的发病机制。
