Lack of Insulin Receptor Substrate-2 Causes Progressive Neointima Formation in Response to Vessel Injury

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Abstract
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−/−...