Natsumi Y, Kashimata M, Hiramatsu M
Meikai Daigaku Shigaku Zasshi. 1989;18(1):21-36.
Epidermal growth factor (EGF) is now well known as a potent mitogen and differentiation factor for a variety of cells both in vivo and in vitro. Like other polypeptide hormones, EGF initially binds to a specific plasma membrane receptor on the target cells. In this study, we investigated the effect of streptozotocin-induced diabetes on EGF receptors on rat liver plasma membranes. An apparent increase in serum glucose concentration was observed in diabetic rats, and treatment of diabetic animals with insulin normalized the glucose concentration to the control level. There was no marked difference in hepatic membrane markers among the control, diabetic and insulin-treated diabetic animals, as judged by protein, sialic acid contents, and phosphodiesterase I and 5'-nucleotidase activities. The binding of 125I-EGF to membranes was found to be significantly lower in diabetic than in control animals. The value in diabetic animals was about 55% of the control level. Insulin treatment of diabetic animals restored the binding of 125I-EGF to the control level, whereas triiodothyronine (T3) treatment had no effect. Scatchard analysis of the binding data clearly showed that the decrease in EGF binding was due to a decrease in the number of receptors rather than to a change in receptor affinity. The decrease in EGF receptor number in diabetic animals was also confirmed by an experiment on affinity labeling of EGF receptors. EGF stimulated the phosphorylation of hepatic EGF receptors (molecular weight = 170,000). The rates of basal and EGF-stimulated phosphorylation of the receptors were lower in diabetic than in control animals. Insulin treatment of diabetic animals restored the phosphorylation activity to control level, whereas T3 treatment had no apparent effect. There was no significant difference in serum EGF concentration among the control, diabetic and insulin-treated diabetic animals. These results indicate that insulin deficiency in vivo causes a decrease in hepatic EGF receptor number, and suggest that the actions of EGF on hepatocytes may also be affected by diabetes mellitus since the effects of EGF are receptor-mediated.
表皮生长因子（EGF）如今作为一种在体内和体外对多种细胞都具有强大促有丝分裂和分化作用的因子而广为人知。与其他多肽激素一样，EGF最初与靶细胞上的特定质膜受体结合。在本研究中，我们调查了链脲佐菌素诱导的糖尿病对大鼠肝质膜上EGF受体的影响。在糖尿病大鼠中观察到血清葡萄糖浓度明显升高，用胰岛素治疗糖尿病动物可使葡萄糖浓度恢复到对照水平。根据蛋白质、唾液酸含量以及磷酸二酯酶I和5'-核苷酸酶活性判断，对照、糖尿病和胰岛素治疗的糖尿病动物之间的肝膜标志物没有显著差异。发现糖尿病动物中125I-EGF与膜的结合明显低于对照动物。糖尿病动物中的值约为对照水平的55%。用胰岛素治疗糖尿病动物可使125I-EGF的结合恢复到对照水平，而用三碘甲状腺原氨酸（T3）治疗则没有效果。对结合数据进行Scatchard分析清楚地表明，EGF结合的减少是由于受体数量的减少而不是受体亲和力的改变。糖尿病动物中EGF受体数量的减少也通过EGF受体亲和标记实验得到证实。EGF刺激肝EGF受体（分子量 = 170,000）的磷酸化。糖尿病动物中受体的基础磷酸化率和EGF刺激的磷酸化率均低于对照动物。用胰岛素治疗糖尿病动物可使磷酸化活性恢复到对照水平，而T3治疗没有明显效果。对照、糖尿病和胰岛素治疗的糖尿病动物之间的血清EGF浓度没有显著差异。这些结果表明体内胰岛素缺乏导致肝EGF受体数量减少，并提示由于EGF的作用是由受体介导的，糖尿病可能也会影响EGF对肝细胞的作用。
