Lack of insulin receptor substrate-2 causes progressive neointima formation in response to vessel injury
Lack of insulin receptor substrate-2 causes progressive neointima formation in response to vessel injury
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DOI：
10.1161/01.cir.0000070937.52035.25
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发表时间：
2003-06-24
期刊：
影响因子：
37.8
通讯作者：
Yamaguchi, T
中科院分区：
文献类型：
--
作者：
Kubota, T;Kubota, N;Yamaguchi, T
背景-胰岛素抵抗与动脉粥样硬化有关，但其机制尚不清楚.据报道，胰岛素受体底物（IRS）-1缺陷（IRS-1（-/-））小鼠显示胰岛素抵抗，而没有2型糖尿病，而IRS-2缺陷（IRS-2（-/-））小鼠显示胰岛素抵抗与2型diabetes.Methods和结果-我们调查了新生内膜形成的IRS-1（-/-）和IRS- 2（-/-）小鼠在8和20周。IRS- 2（-/-）小鼠在8周时显示出比IRS-1（-/-）和野生型小鼠大得多的新生内膜形成。在20周时，IRS-2（-/-）小鼠比IRS-1（-/-）小鼠具有更大的新生内膜形成，IRS-1（-/-）小鼠显示比野生型小鼠更多的新生内膜形成. IRS-1（-/-）和IRS-2（-/-）小鼠存在血脂异常、高血压和胰岛素抵抗。IRS-2（-/-）小鼠在8周和20周时比IRS-1（-/-）小鼠有更多的代谢异常。IRS- 2的表达被检测到，但IRS- 1的表达未被检测到在vessel.Conclusions -在IRS-1（-/-）和IRS-2（-/-）小鼠的新生内膜的形成似乎是相关的异常诱导的胰岛素抵抗状态的代谢环境的改变。此外，由于在第8周和第20周时IRS-2（-/-）小鼠中的新生内膜形成比IRS-1（-/-）小鼠中的新生内膜形成大得多，这表明IRS- 2的缺乏使得血管系统在异常代谢环境中更容易受到损伤，并且IRS- 2可能对新生内膜形成具有保护作用。我们的结论是，IRS- 2是保护和延缓胰岛素抵抗状态下的新生内膜形成的发展。
Background - Insulin resistance is associated with atherosclerosis, but its mechanism is unknown. It has been reported that insulin receptor substrate (IRS)-1 deficient (IRS-1(-/-)) mice showed insulin resistance without type 2 diabetes, whereas the IRS-2 deficient (IRS-2(-/-)) mice showed insulin resistance with type 2 diabetes.Methods and Results - We investigated neointima formation in the IRS-1(-/-) and IRS- 2(-/-) mice at 8 and 20 weeks. The IRS- 2(-/-) mice showed much greater neointima formation than the IRS-1(-/-) and wild- type mice at 8 weeks. At 20 weeks, the IRS-2(-/-) mice had greater neointima formation than the IRS-1(-/-) mice, which showed more enhanced neointima formation than the wild- type mice. The IRS-1(-/-) and IRS-2(-/-) mice had dyslipidemia, hypertension, and insulin resistance. The IRS-2(-/-) mice had more metabolic abnormalities than the IRS-1(-/-) mice at 8 and 20 weeks. IRS- 2 expression was detected, but IRS- 1 expression was not detected in the vessels.Conclusions - The neointima formation in the IRS-1(-/-) and IRS-2(-/-) mice appears to be related to abnormalities induced by the altered metabolic milieu in insulin-resistant states. Moreover, because neointima formation was much greater in the IRS-2(-/-) mice than in the IRS-1(-/-) mice at 8 and 20 weeks, it is suggested that a lack of IRS- 2 renders the vasculature more susceptible to injury in the abnormal metabolic milieu, and IRS- 2 may have a protective effect on neointima formation. We conclude that IRS- 2 is protective and retards the development of neointima formation in insulin-resistant states.