Morishige W K, Uetake C A, Greenwood F C, Akaka J
Endocrinology. 1977 Jun;100(6):1710-22. doi: 10.1210/endo-100-6-1710.
Adult rats were rendered diabetic by a single iv injection of streptozotocin (70 or 75 mg/kg). In these rats, serum insulin fell to minimal levels during the 48 h following drug treatment, and this was roughly paralleled by a progressive decrease in the ability of the lung to oxidize glucose. The addition of insulin to diabetic rat lung slices in vitro had no restorative effect on the depressed glucose oxidative rate during a 2 h incubation period; however, two daily treatments of the rats with 1 unit of protamine, zinc insulin completely restored lung glucose oxidation rate to normal, without significantly reducing the hyperglycemic state of the rats. An examination of the temporal changes in glucose utilization by the rat lung after acute insulin treatment revealed that the diabetic lung responded directly to serum levels of insulin, whereas the normal lung appeared to be unaffected by serum insulin levels as hihg as 87 ng/ml. The reduced rate of glucose oxidation in the diabetic lung was apparent after perfusion of the lung with glucose-free medium, and was characterized by a significant reduction in Vmax without an alteration in Km. This was attended by a depressed ability of the lung to incorporate [3H]leucine into protein and an increased ability to produce lactate, but hexose monophosphate shunt activity was normal. Specific receptors for insulin have been identified and partially characterized in crude membrane preparations of normal rat lung. The interaction of insulin with these receptors was rapid, reversible, saturable, and was dependent upon time and temperature. The binding of labeled insulin was inhibited by low concentrations of unlabeled insulin and by high concentrations of proinsulin, whereas it was unaffected by the presence of glucagon, gastrin, prolactin, ACTH, or growth hormone in microgram amounts. These observations suggest that insulin regulates the transport and utilization of glucose in the rat lung, and that this tissue contains specific receptors for insulin.
成年大鼠通过单次静脉注射链脲佐菌素（70或75毫克/千克）诱导糖尿病。在这些大鼠中，药物治疗后的48小时内血清胰岛素降至最低水平，同时肺氧化葡萄糖的能力也相应逐渐下降。体外向糖尿病大鼠肺切片中添加胰岛素在2小时的孵育期内对降低的葡萄糖氧化速率没有恢复作用；然而，每天给大鼠注射1单位的精蛋白锌胰岛素，连续两天治疗可使肺葡萄糖氧化速率完全恢复正常，且不会显著降低大鼠的高血糖状态。对急性胰岛素治疗后大鼠肺葡萄糖利用的时间变化进行检查发现，糖尿病肺直接对血清胰岛素水平作出反应，而正常肺在血清胰岛素水平高达87纳克/毫升时似乎不受影响。用无葡萄糖培养基灌注肺后，糖尿病肺中葡萄糖氧化速率降低明显，其特征是最大反应速度（Vmax）显著降低而米氏常数（Km）不变。同时，肺将[3H]亮氨酸掺入蛋白质的能力下降，产生乳酸的能力增强，但磷酸己糖旁路活性正常。在正常大鼠肺的粗膜制剂中已鉴定出胰岛素的特异性受体并对其进行了部分特性描述。胰岛素与这些受体的相互作用迅速、可逆、可饱和，且依赖于时间和温度。低浓度的未标记胰岛素和高浓度的胰岛素原可抑制标记胰岛素的结合，而微克量的胰高血糖素、胃泌素、催乳素、促肾上腺皮质激素或生长激素的存在对其无影响。这些观察结果表明，胰岛素调节大鼠肺中葡萄糖的转运和利用，且该组织含有胰岛素的特异性受体。
