Division of Translational Biology, the Hamner Institutes for Health Sciences, Durham, NC 27709, USA.
Curr Mol Pharmacol. 2011 Nov;4(3):154-66. doi: 10.2174/1874467211104030154.
The main goal of this review is to provide more specific and effective targets for prevention and treatment of insulin resistance and associated atherosclerosis. Modern technologies and medicine have vastly improved human health and prolonged the average life span of humans primarily by eliminating various premature deaths and infectious diseases. The modern technologies have also provided us abundant food and convenient transportation tools such as cars. As a result, more people are becoming overfed and sedentary. People are generally ingesting more calories than their bodies' need, leading to the so-called "positive energy imbalance", which is inseparable from the development of insulin resistance and its associated atherosclerosis. A direct consequence of insulin resistance is hyperinsulinemia. The current general view is that insulin is not functional properly in the presence of insulin resistance. Thus, the role of insulin itself in the development of insulin resistance and associated atherosclerosis has not been recognized. We have recently observed that the basal level of insulin signaling is increased in the presence of insulin resistance and hyperinsulinemia. In this review, we will explain how the increased basal insulin signaling contributes to the development of insulin resistance and associated atherosclerosis. We will first explain how insulin causes insulin resistance through two arbitrary stages (before and after the presence of obvious insulin resistance), and, then, explain how the excess exposure to insulin and the relative insulin insufficiency contributes to the atherosclerotic diseases. We propose that blockade of the excess insulin signaling is a viable approach to prevent and/or reverse insulin resistance and its associated atherosclerosis.
本综述的主要目的是为胰岛素抵抗和相关动脉粥样硬化的预防和治疗提供更具体、更有效的靶点。现代技术和医学通过消除各种早逝和传染病，极大地改善了人类健康，延长了人类的平均寿命。现代技术还为我们提供了丰富的食物和便捷的交通工具，如汽车。结果，越来越多的人变得营养过剩和久坐不动。人们摄入的卡路里通常超过身体的需要，导致所谓的“正能量失衡”，这与胰岛素抵抗及其相关动脉粥样硬化的发展密不可分。胰岛素抵抗的直接后果是高胰岛素血症。目前的普遍观点认为，在存在胰岛素抵抗的情况下，胰岛素不能正常发挥作用。因此，胰岛素本身在胰岛素抵抗和相关动脉粥样硬化发展中的作用尚未得到认识。我们最近观察到，在存在胰岛素抵抗和高胰岛素血症的情况下，胰岛素信号的基础水平增加。在这篇综述中，我们将解释基础胰岛素信号的增加如何导致胰岛素抵抗和相关动脉粥样硬化的发展。我们将首先解释胰岛素如何通过任意两个阶段（明显胰岛素抵抗之前和之后）导致胰岛素抵抗，然后解释过多的胰岛素暴露和相对胰岛素不足如何导致动脉粥样硬化疾病。我们提出，阻断过量的胰岛素信号是预防和/或逆转胰岛素抵抗及其相关动脉粥样硬化的可行方法。
