Kergoat M, Simon J, Portha B
Lab. Physiol. Dev., CNRS UA 307, Université Paris 7, France.
Biochem Biophys Res Commun. 1988 May 16;152(3):1015-22. doi: 10.1016/s0006-291x(88)80385-1.
Using the insulin-glucose clamp technique, we have previously shown that an increased sensitivity to insulin in vivo is a characteristic of the liver in rats with non-insulin-dependent diabetes induced by neonatal streptozotocin administration. We have thus studied the properties of liver insulin receptor in that model. 125I-porcine insulin binding was found normal both in isolated plasma membranes and in solubilized, wheat germ agglutinin purified receptors prepared from livers of rats with non-insulin-dependent diabetes, when compared to controls. Basal and insulin-stimulated insulin receptor kinase activities were also found normal for both the autophosphorylation of the beta subunit of the insulin receptor and the phosphorylation of the artificial substrate poly (Glu-Tyr) 4:1. Thus, in that model of chronic insulin deficiency and mild hyperglycemia: 1) liver insulin receptors are not up-regulated; 2) tyrosine kinase activity remains unaffected. This last observation supports the hypothesis that the increased insulin effect in the liver of rats with non-insulin-dependent diabetes is probably distal to the insulin receptor kinase.
运用胰岛素-葡萄糖钳夹技术，我们先前已表明，体内对胰岛素敏感性增加是新生期注射链脲佐菌素诱导的非胰岛素依赖型糖尿病大鼠肝脏的一个特征。因此，我们研究了该模型中肝脏胰岛素受体的特性。与对照组相比，在非胰岛素依赖型糖尿病大鼠肝脏制备的分离质膜以及经溶解、麦胚凝集素纯化的受体中，发现¹²⁵I-猪胰岛素结合正常。对于胰岛素受体β亚基的自身磷酸化以及人工底物聚（谷氨酸-酪氨酸）4:1的磷酸化，基础和胰岛素刺激的胰岛素受体激酶活性也均正常。因此，在这种慢性胰岛素缺乏和轻度高血糖模型中：1）肝脏胰岛素受体未上调；2）酪氨酸激酶活性未受影响。最后这一观察结果支持了这样的假说，即非胰岛素依赖型糖尿病大鼠肝脏中胰岛素作用增强可能发生在胰岛素受体激酶的下游。
