Reaven G M
Department of Medicine, Stanford University Medical Center, California.
Diabetes. 1988 Dec;37(12):1595-607. doi: 10.2337/diab.37.12.1595.
Resistance to insulin-stimulated glucose uptake is present in the majority of patients with impaired glucose tolerance (IGT) or non-insulin-dependent diabetes mellitus (NIDDM) and in approximately 25% of nonobese individuals with normal oral glucose tolerance. In these conditions, deterioration of glucose tolerance can only be prevented if the beta-cell is able to increase its insulin secretory response and maintain a state of chronic hyperinsulinemia. When this goal cannot be achieved, gross decompensation of glucose homeostasis occurs. The relationship between insulin resistance, plasma insulin level, and glucose intolerance is mediated to a significant degree by changes in ambient plasma free-fatty acid (FFA) concentration. Patients with NIDDM are also resistant to insulin suppression of plasma FFA concentration, but plasma FFA concentrations can be reduced by relatively small increments in insulin concentration. Consequently, elevations of circulating plasma FFA concentration can be prevented if large amounts of insulin can be secreted. If hyperinsulinemia cannot be maintained, plasma FFA concentration will not be suppressed normally, and the resulting increase in plasma FFA concentration will lead to increased hepatic glucose production. Because these events take place in individuals who are quite resistant to insulin-stimulated glucose uptake, it is apparent that even small increases in hepatic glucose production are likely to lead to significant fasting hyperglycemia under these conditions. Although hyperinsulinemia may prevent frank decompensation of glucose homeostasis in insulin-resistant individuals, this compensatory response of the endocrine pancreas is not without its price. Patients with hypertension, treated or untreated, are insulin resistant, hyperglycemic, and hyperinsulinemic. In addition, a direct relationship between plasma insulin concentration and blood pressure has been noted. Hypertension can also be produced in normal rats when they are fed a fructose-enriched diet, an intervention that also leads to the development of insulin resistance and hyperinsulinemia. The development of hypertension in normal rats by an experimental manipulation known to induce insulin resistance and hyperinsulinemia provides further support for the view that the relationship between the three variables may be a causal one.(ABSTRACT TRUNCATED AT 400 WORDS)
大多数糖耐量受损（IGT）患者或非胰岛素依赖型糖尿病（NIDDM）患者以及约25%口服葡萄糖耐量正常的非肥胖个体存在对胰岛素刺激的葡萄糖摄取的抵抗。在这些情况下，只有当β细胞能够增加其胰岛素分泌反应并维持慢性高胰岛素血症状态时，糖耐量的恶化才能得到预防。当这个目标无法实现时，葡萄糖稳态就会出现严重失代偿。胰岛素抵抗、血浆胰岛素水平和葡萄糖不耐受之间的关系在很大程度上是由周围血浆游离脂肪酸（FFA）浓度的变化介导的。NIDDM患者对胰岛素抑制血浆FFA浓度也有抵抗，但血浆FFA浓度可通过胰岛素浓度相对较小的增加而降低。因此，如果能分泌大量胰岛素，循环血浆FFA浓度的升高就可以得到预防。如果不能维持高胰岛素血症，血浆FFA浓度就不能正常被抑制，由此导致的血浆FFA浓度升高将导致肝葡萄糖生成增加。由于这些事件发生在对胰岛素刺激的葡萄糖摄取有相当抵抗的个体中，很明显，在这些情况下，即使肝葡萄糖生成的小幅增加也可能导致明显的空腹高血糖。虽然高胰岛素血症可能会防止胰岛素抵抗个体出现明显的葡萄糖稳态失代偿，但内分泌胰腺的这种代偿反应并非没有代价。无论是否接受治疗，高血压患者都存在胰岛素抵抗、高血糖和高胰岛素血症。此外，还注意到血浆胰岛素浓度与血压之间存在直接关系。当正常大鼠喂食富含果糖的饮食时也会产生高血压，这种干预也会导致胰岛素抵抗和高胰岛素血症的发展。通过一种已知会诱导胰岛素抵抗和高胰岛素血症的实验操作在正常大鼠中诱发高血压，为这三个变量之间的关系可能是因果关系这一观点提供了进一步的支持。（摘要截选至400字）
