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Inducible nitric oxide synthase and insulin resistance.

学友会セミナー

学友会セミナー

2002年開催 学友会セミナー

開催日時: 2002年2月20日(水)16:00 ~ 17:00
開催場所: 東京大学医科学研究所 アムジェンホール大会議室
講  師: Dr. Masao Kaneki
所  属: Massachusetts General Hospital, Harvard Medical School, USA
演  題: Inducible nitric oxide synthase and insulin resistance.
概  要:

Molecular mechanisms responsible for insulin resistance, which is the major causal factor for type 2 diabetes, still remains elusive, in spite of the intensive investigation of the number of years. Nitric oxide (NO) is synthesized from arginine and O2 and by three major NO synthase isoenzymes. Endothelial and neuronal NO synthases are constitutively expressed in endothelial cells and neurons and generate small amounts of NO. On the other hand, inducible NO synthase (iNOS) can be induced by pro-inflammatory cytokines and stress conditions in macrophages and in many cell types, including skeletal muscle cells, adipocytes and hepatocytes, and generates NO to much greater extent (up to 1000-fold). The actions of NO can be classified by two category; namely, (1) cGMP-dependent effects of NO, which is well exemplified by NO-mediated vasodilation, and (2) cGMP-independent, nitrosative posttranslational modification (e.g., S-nitrosylation, tyrosine nitration)-involved effects. iNOS and nitrosative stress have been implicated in many human diseases including inflammation, nuerodegenerative disorders, atherosclerosis and cancer. The accumulating evidence suggests a close biological link between iNOS and insulin resistance. However, little is known about a potential role for iNOS in the pathogenesis of obesity-and stress- induced insulin resistance. We have been garnering the in vivo and in vitro evidence indicating a pivotal role for iNOS. The gene disruption of iNOS results in the protection from both obesity- and stress-associated insulin resistance. The components of insulin signal transduction pathway are the targets of nitrosative posttranslational modifications in vivo in genetically obese, diabetic (db/db) mice and in rats administered with burn injury or endotoxin (LPS). The impact of nitrosative stress on insulin signaling will be discussed.

世 話 人: 森 茂郎
古川 洋一