Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture.
Selective Insulin Resistance and the Development of Cardiovascular Diseases in Diabetes: The 2015 Edwin Bierman Award Lecture.
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作者：
King GL;Park K;Li Q
埃德温·比尔曼奖讲座是为了纪念埃德温·比尔曼博士，他是糖尿病、肥胖、高脂血症和动脉粥样硬化领域的杰出科学家、导师和领导者。该奖项和讲座旨在表彰大血管并发症和糖尿病危险因素领域的领先科学家。George L. King，医学博士，血管细胞生物学和并发症科，Dianne Nunnally Hoppes糖尿病并发症实验室，乔斯林糖尿病中心，哈佛医学院，波士顿，马萨诸塞州，在美国糖尿病协会第75届科学会议上获得了著名的奖项，2015年6月5日至9日，在波士顿，马萨诸塞州。2015年6月7日，他在埃德温·比尔曼奖上发表了题为“选择性胰岛素抵抗和糖尿病心血管疾病的发展”的演讲。本文综述了引起各种心血管疾病的因素和潜在机制。在糖尿病中，胰岛素对内皮和其他血管细胞的作用对全身代谢和心血管病理的发展有重要影响。我们的研究表明，内皮上的胰岛素受体对胰岛素通过内皮屏障的转运和调节胰岛素在肌肉、心脏、脂肪和大脑中的作用很重要。胰岛素对血管细胞的作用可通过IRS/PI3K/Akt或Grb/Shc/MAPK两种通路介导。胰岛素激活IRS/PI3K/Akt的主要作用是抗动脉粥样硬化，这一途径诱导eNOS的激活，HO-1和VEGF的表达，以及VCAM-1的减少。相反，胰岛素激活Grb/Shc/MAPK通路介导ET-1和PAI-1的表达以及收缩细胞的迁移和增殖，具有促动脉粥样硬化作用。糖尿病和胰岛素抵抗引起的葡萄糖、游离脂肪酸和炎症细胞因子水平升高选择性地抑制胰岛素通过IRS/PI3K/Akt通路的抗动脉粥样硬化作用。本综述提供的证据支持胰岛素在预防心血管病理中的重要性，这种作用可以通过糖尿病的IRS/PI3K/Akt级联选择性抑制。
The Edwin Bierman Award Lecture is presented in honor of the memory of Edwin L. Bierman, MD, an exemplary scientist, mentor, and leader in the field of diabetes, obesity, hyperlipidemia, and atherosclerosis. The award and lecture recognizes a leading scientist in the field of macrovascular complications and contributing risk factors in diabetes. George L. King, MD, of the Section of Vascular Cell Biology and Complications, Dianne Nunnally Hoppes Laboratory for Diabetes Complications, Joslin Diabetes Center, Harvard Medical School, Boston, MA, received the prestigious award at the American Diabetes Association’s 75th Scientific Sessions, 5–9 June 2015, in Boston, MA. He presented the Edwin Bierman Award Lecture, “Selective Insulin Resistance and the Development of Cardiovascular Disease in Diabetes,” on Sunday, 7 June 2015. This review is focused on the factors and potential mechanisms that are causing various cardiovascular pathologies. In diabetes, insulin’s actions on the endothelium and other vascular cells have significant influence on systemic metabolisms and the development of cardiovascular pathologies. Our studies showed that insulin receptors on the endothelium are important for insulin transport across the endothelial barrier and mediate insulin’s actions in muscle, heart, fat, and the brain. Insulin actions on the vascular cells are mediated by two pathways involving the actions of either IRS/PI3K/Akt or Grb/Shc/MAPK. Insulin’s activation of IRS/PI3K/Akt results in mostly antiatherogenic actions, as this pathway induces activation of eNOS, the expressions of HO-1 and VEGF, and the reduction of VCAM-1. In contrast, insulin’s activation of the Grb/Shc/MAPK pathway mediates the expressions of ET-1 and PAI-1 and migration and proliferation of contractile cells, which have proatherogenic actions. Elevated levels of glucose, free fatty acids, and inflammatory cytokines due to diabetes and insulin resistance selectively inhibit insulin’s antiatherogenic actions via the IRS/PI3K/Akt pathway. This review provides evidence to support the importance of insulin actions in preventing cardiovascular pathology that can be selectively inhibited via the IRS/PI3K/Akt cascade in diabetes.