Rossetti L, Giaccari A, DeFronzo R A
Department of Medicine, University of Texas Health, San Antonio 78284.
Diabetes Care. 1990 Jun;13(6):610-30. doi: 10.2337/diacare.13.6.610.
Glucose toxicity is a well-established entity that has been shown in animal models of diabetes to contribute to development of insulin resistance and impaired insulin secretion. In type II (non-insulin-dependent) diabetes in humans, a considerable body of evidence has accumulated indicating that a chronic physiological increment in the plasma glucose concentration leads to progressive impairment in insulin secretion and may contribute to insulin resistance as well. The precise biochemical mechanism(s) responsible for the hyperglycemia-induced defect in insulin secretion remains to be defined but may be related to a defect in phosphoinositide metabolism. In animal models of diabetes, development of insulin resistance is related to downregulation of the glucose-transport system, and a similar phenomenon is also likely to occur in humans. In addition, hyperglycemia in humans may lead to a defect in glycogen synthesis. In this respect, humans may be different from rats. In type I (insulin-dependent) diabetic patients who are poorly controlled, insulin resistance is a characteristic feature and can be ameliorated by tight glycemic control, suggesting that hyperglycemia is responsible for the insulin resistance. Evidence also has accumulated to implicate glucose toxicity in the functional impairment in insulin secretion that occurs during the initial presentation of patients with type I diabetes, and this may explain the honeymoon period so commonly observed after the institution of insulin therapy.
葡萄糖毒性是一个已被充分证实的现象，在糖尿病动物模型中已表明它会导致胰岛素抵抗的发展和胰岛素分泌受损。在人类的II型（非胰岛素依赖型）糖尿病中，大量证据已经积累起来，表明血浆葡萄糖浓度的慢性生理性升高会导致胰岛素分泌逐渐受损，并且也可能导致胰岛素抵抗。导致高血糖诱导的胰岛素分泌缺陷的确切生化机制仍有待确定，但可能与磷酸肌醇代谢缺陷有关。在糖尿病动物模型中，胰岛素抵抗的发展与葡萄糖转运系统的下调有关，类似的现象在人类中也可能发生。此外，人类的高血糖可能导致糖原合成缺陷。在这方面，人类可能与大鼠不同。在控制不佳的I型（胰岛素依赖型）糖尿病患者中，胰岛素抵抗是一个特征性表现，并且可以通过严格的血糖控制得到改善，这表明高血糖是胰岛素抵抗的原因。也有证据表明葡萄糖毒性与I型糖尿病患者初诊时出现的胰岛素分泌功能损害有关，这可能解释了胰岛素治疗开始后常见的蜜月期。
