Reaven G M
Department of Medicine, Stanford University School of Medicine and Geriatric Research, Department of Veterans Affairs Medical Center, Palo Alto, California, USA.
Physiol Rev. 1995 Jul;75(3):473-86. doi: 10.1152/physrev.1995.75.3.473.
The ability of insulin to stimulate glucose uptake varies widely from person to person, and these differences, as well as how the individual attempts to compensate for them, are of fundamental importance in the development and clinical course of what are often designated as diseases of Western civilization. Evidence is presented that non-insulin-dependent diabetes mellitus (NIDDM) results from a failure on the part of pancreatic beta-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. In addition, a coherent formulation of the physiological changes that lead from the defect in cellular insulin action to the loss in glucose homeostasis is presented. However, the ability to maintain the degree of compensatory hyperinsulinemia necessary to prevent loss of glucose tolerance in insulin-resistant individuals does not represent an unqualified homeostatic victory. In contrast, evidence is presented supporting the view that the combination of insulin resistance and compensatory hyperinsulinemia predisposes to the development of a cluster of abnormalities, including some degree of glucose intolerance, an increase in plasma triglyceride and a decrease in high-density lipoprotein cholesterol concentrations, high blood pressure, hyperuricemia, smaller denser low-density lipoprotein particles, and higher circulating levels of plaminogen activator inhibitor 1. The cluster of changes associated with insulin resistance has been said to comprise syndrome X, and all of the manifestations of syndrome X have been shown to increase risk of coronary heart disease. Thus it is concluded that insulin resistance and its associated abnormalities are of utmost importance in the pathogenesis of NIDDM, hypertension, and coronary heart disease.
胰岛素刺激葡萄糖摄取的能力在个体之间差异很大，这些差异以及个体如何试图代偿这些差异，在通常被称为西方文明病的发生和临床过程中至关重要。有证据表明，非胰岛素依赖型糖尿病（NIDDM）是由于胰腺β细胞未能充分代偿胰岛素抵抗个体中胰岛素作用的缺陷所致。此外，还提出了从细胞胰岛素作用缺陷到葡萄糖稳态丧失的生理变化的连贯表述。然而，维持胰岛素抵抗个体中防止葡萄糖耐量丧失所需的代偿性高胰岛素血症程度的能力并不代表完全的稳态胜利。相反，有证据支持这样的观点，即胰岛素抵抗和代偿性高胰岛素血症共同作用易引发一系列异常，包括一定程度的葡萄糖不耐受、血浆甘油三酯升高、高密度脂蛋白胆固醇浓度降低、高血压、高尿酸血症、较小且致密的低密度脂蛋白颗粒以及纤溶酶原激活物抑制剂1循环水平升高。与胰岛素抵抗相关的一系列变化被称为X综合征，并且已表明X综合征的所有表现都会增加冠心病风险。因此得出结论，胰岛素抵抗及其相关异常在NIDDM、高血压和冠心病的发病机制中至关重要。
