Zeleznik A J, Roth J
J Clin Invest. 1978 May;61(5):1363-74. doi: 10.1172/JCI109054.
Based on studies of the interaction of insulin with its receptors in vitro, we calculated that a receptor compartment should be measurable directly in vivo. For this purpose, rabbits were injected intravenously with a labeled insulin that has low affinity for receptors in combination with a radioiodinated insulin that has high affinity for receptors. Plasma concentrations of labeled insulins were measured at selected intervals after injection. Apparent volumes of distribution were calculated by extrapolation of plasma distribution were calculated by extrapolation of plasma disappearance curves; high affinity insulins consistently distributed into spaces that were two-three times greater than those of the low affinity insulins. Injections of unlabeled pork insulin before tracer insulins decreased the distribution space of the high affinity insulin in a dose-dependent manner while having little or no effect on the distribution space of the low affinity labeled insulin. When unlabeled insulin was injected after the tracer insulins, there was an immediate rise in the plasma concentration of the high affinity insulin with only a slight change in the plasma concentration of the low affinity insulin. These results demonstrate that high affinity insulins distribute into a body compartment which has many properties of the insulin receptor previously studied in vitro. This receptor compartment: (a) recognizes insulins based on their biological potencies; (b) is saturated by elevated concentrations of insulin; and (c) insulin bound to receptors is in equilibrium with free hormone in plasma. Further, the bound to free ratios for hormone, calculated from these data, suggest that in vivo greater than 50% of the extrapancreatic insulin is bound to receptors during normal physiological states.
基于胰岛素与其受体在体外相互作用的研究，我们计算出受体区室应该可以在体内直接测量。为此，给兔子静脉注射对受体亲和力低的标记胰岛素，并结合对受体亲和力高的放射性碘化胰岛素。在注射后选定的时间间隔测量标记胰岛素的血浆浓度。通过血浆消失曲线的外推计算表观分布容积；高亲和力胰岛素始终分布到比低亲和力胰岛素大三倍的空间中。在注射示踪胰岛素之前注射未标记的猪胰岛素，以剂量依赖的方式降低了高亲和力胰岛素的分布空间，而对低亲和力标记胰岛素的分布空间几乎没有影响或没有影响。当在示踪胰岛素之后注射未标记的胰岛素时，高亲和力胰岛素的血浆浓度立即升高，而低亲和力胰岛素的血浆浓度仅有轻微变化。这些结果表明，高亲和力胰岛素分布到一个具有许多先前在体外研究的胰岛素受体特性的体内区室。这个受体区室：（a）根据胰岛素的生物活性识别胰岛素；（b）被升高的胰岛素浓度饱和；（c）与受体结合的胰岛素与血浆中的游离激素处于平衡状态。此外，根据这些数据计算的激素结合与游离比率表明，在正常生理状态下，体内超过50%的胰腺外胰岛素与受体结合。
