Tominaga M, Yamatani K, Igarashi M, Eguchi H, Daimon M, Sekikawa A, Sasaki H
Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
Endocr J. 1995 Jun;42(3):397-403. doi: 10.1507/endocrj.42.397.
The metabolic effect of recombinant human insulin-like growth factor I (IGF-I) was investigated by the glucose clamp technique in normal rats and streptozotocin-induced diabetic rats, a model of insulin-dependent diabetes mellitus (IDDM), and compared with that of insulin. Glucose uptake by peripheral tissues was stimulated by intravenous administration of IGF-I at rates of from 0.369 to 3.690 nmol/kg/min in a dose dependent manner, with a potency of 1/52 that of insulin estimated on the basis of the ED50 molar ratio in normal rats. In streptozotocin-induced diabetic rats, the maximum effects of IGF-I and insulin were reduced to 72% and 70% of those in normal rats, respectively, indicating the presence of both IGF-I and insulin resistance. Hepatic glucose output in normal rats was suppressed by IGF-I in a dose dependent manner with a weaker potency of 1/99 that of insulin assessed on the basis of the ED50 values. In streptozotocin-induced diabetic rats, a dose-response curve of the suppressive effect of insulin on hepatic glucose output shifted to the right, indicating the presence of hepatic insulin resistance, but a leftward shifting of the suppressive effect of IGF-I on hepatic glucose output was observed. We concluded that the IGF-I effect on peripheral tissue was decreased but that on the liver was rather increased in streptozotocin-induced diabetic rats, in contrast to the resistance of both peripheral tissues and liver to insulin.
采用葡萄糖钳夹技术研究了重组人生长激素释放因子I（IGF-I）在正常大鼠和链脲佐菌素诱导的糖尿病大鼠（胰岛素依赖型糖尿病（IDDM）模型）中的代谢效应，并与胰岛素的效应进行了比较。静脉注射IGF-I后，外周组织的葡萄糖摄取以剂量依赖方式受到刺激，速率为0.369至3.690 nmol/kg/min，根据正常大鼠的ED50摩尔比估计，其效力为胰岛素的1/52。在链脲佐菌素诱导的糖尿病大鼠中，IGF-I和胰岛素的最大效应分别降至正常大鼠的72%和70%，表明存在IGF-I和胰岛素抵抗。在正常大鼠中，IGF-I以剂量依赖方式抑制肝脏葡萄糖输出，根据ED50值评估，其效力较弱，为胰岛素的1/99。在链脲佐菌素诱导的糖尿病大鼠中，胰岛素对肝脏葡萄糖输出的抑制作用的剂量反应曲线向右移动，表明存在肝脏胰岛素抵抗，但观察到IGF-I对肝脏葡萄糖输出的抑制作用向左移动。我们得出结论，与外周组织和肝脏对胰岛素的抵抗相反，在链脲佐菌素诱导的糖尿病大鼠中，IGF-I对外周组织的作用降低，但对肝脏的作用反而增强。
