Ueki A
Nihon Naibunpi Gakkai Zasshi. 1980 Jan 20;56(1):15-26. doi: 10.1507/endocrine1927.56.1_15.
In order to elucidate the mechanism of hyperinsulinism following a treatment with glucocorticoid, insulin secretion induced with glucose or tolbutamide was investigated by a perifusion experiment on isolated islets of rats. The results are summarized as follows: 1. The fasting blood glucose level was significantly higher on the 2nd day (174.0 +/- 11.8 mg/dl) and 3rd day (179.6 +/- 9.5 mg/dl) in the glucocorticoid treated rats, than it was in the control rats (129.0 +/- 12.0 mg/dl). The serum insulin levels began to increase from the first day following the glucocorticoid treatment (17.2 +/- 1.3 microU/ml in the control rats, 27.6 +/- 2.1 microU/ml on the 1st day, 32.4 +/- 3.9 microU/ml on the 2nd day, and 34.5 +/- 1.4 microU/ml on the 3rd day). 2. The insulin content of the islets decreased with the glucocorticoid treatment (765.6 +/- 34.5 microU/islet in the control rat, 576.6 +/- 25.0 microU/islet on the 1st day, 629.2 +/- 36.9 microU/islet on the 2nd day, and 482.0 +/- 43.5 microU/islet on the 3rd day). 3. In the perifusion experiment, a biphasic pattern of insulin secretion was demonstrated with the stimulation of glucose in the control and glucocorticoid treated rats. A remarkable enhancement of insulin secretion was observed by the stimulation of 100 mg/dl glucose. The amount of insulin secretion at the first phase (up to 7 min. after the glucose stimulation) was 2.9 +/- 0.5 microU/islet on the 1st day, 2.7 +/- 0.3 microU/islet on the 2nd day and 3.8 +/- 0.1 microU/islet on the 3rd day; these amounts were high compared with that of 1.8 +/- 0.1 microU/islet in the control rat. The amount of insulin secretion at the second phase (8 to 60 min. after the glucose stimulation) was 28.5 +/- 2.5 microU/islet on the 1st day, 37.1 +/- 3.3 microU/islet on the 2nd day and 41.3 +/- 1.8 microU/islet on the 3rd day; these amounts were higher when compared with that of 24.7 +/- 0.7 microU/islet in the control rat. 4. The monophasic insulin secretion from isolated islets by the stimulation of tolbutamide was enhanced with the treatment of glucocorticoid. These results indicate that glucocorticoid directly enhances insulin secretion from the pancreatic islets at the physiological concentration of blood glucose, which seems to be an important factor in the occurrence of hyperinsulinemia associated with glucocorticoid therapy.
为阐明糖皮质激素治疗后高胰岛素血症的机制，通过对大鼠分离胰岛的灌注实验，研究了葡萄糖或甲苯磺丁脲诱导的胰岛素分泌。结果总结如下：1. 糖皮质激素治疗组大鼠在第2天（174.0±11.8mg/dl）和第3天（179.6±9.5mg/dl）的空腹血糖水平显著高于对照组大鼠（129.0±12.0mg/dl）。糖皮质激素治疗后第1天血清胰岛素水平开始升高（对照组大鼠为17.2±1.3μU/ml，第1天为27.6±2.1μU/ml，第2天为32.4±3.9μU/ml，第3天为34.5±1.4μU/ml）。2. 随着糖皮质激素治疗，胰岛的胰岛素含量降低（对照组大鼠为765.6±34.5μU/胰岛，第1天为576.6±25.0μU/胰岛，第2天为629.2±36.9μU/胰岛，第3天为482.0±43.5μU/胰岛）。3. 在灌注实验中，对照组和糖皮质激素治疗组大鼠在葡萄糖刺激下均呈现胰岛素分泌的双相模式。100mg/dl葡萄糖刺激可观察到胰岛素分泌显著增强。第一相（葡萄糖刺激后7分钟内）胰岛素分泌量在第1天为2.9±0.5μU/胰岛，第2天为2.7±0.3μU/胰岛，第3天为3.8±0.1μU/胰岛；与对照组大鼠的1.8±0.1μU/胰岛相比，这些值较高。第二相（葡萄糖刺激后8至60分钟）胰岛素分泌量在第1天为28.5±2.5μU/胰岛，第2天为37.1±3.3μU/胰岛，第3天为41.3±1.8μU/胰岛；与对照组大鼠的24.7±0.7μU/胰岛相比，这些值更高。4. 甲苯磺丁脲刺激分离胰岛产生的单相胰岛素分泌在糖皮质激素治疗后增强。这些结果表明，在生理血糖浓度下，糖皮质激素直接增强胰岛的胰岛素分泌，这似乎是糖皮质激素治疗相关高胰岛素血症发生的一个重要因素。
