TNFa変換酵素を介したインスリン抵抗性発現機序の解析

T肿瘤坏死因子（TNF）转换酶（TACE）切割TNF的跨膜前体并产生成熟的TNF， TNF是促炎细胞因子，是肥胖和糖尿病诱导的胰岛素抵抗的主要介质之一。然而，肥胖中TACE活性和胰岛素敏感组织表达的调控尚未完全确定。在本研究中，我们发现肥胖引起KKAy小鼠TACE活性和表达的脂肪组织特异性上调和热量限制引起的下调。此外，我们发现几种应激激酶的激活可能涉及肥胖小鼠脂肪组织中TACE功能的上调。

T umor necrosis factor (TNF) converting enzyme (TACE)cleaves the transmembrane precursor of TNF and produces mature TNF , which is aproinflammatory cytokine and one of the major mediators of obesity- and diabetes-inducedinsulin resistance. However , the regulation of TACE activity and expression ininsulin-sensitive tissues in obesity has not been fully determined. In the presentinvestigation, we found the adipose tissue-specific upregulation of TACE activity andexpression induced by obesity and the downregulation by caloric restriction in KKAy mice.In addition, we found that the activation of several stress-kinases may involve in theupreglation of TACE function in adipose tissue of obese mice.