Ciaraldi T P, Brady D
Veterans Administration Medical Center, Medical Research Service, San Diego, California.
Horm Metab Res. 1990 May;22(5):283-8. doi: 10.1055/s-2007-1004903.
The binding and biologic potencies as well as kinetics of action of human biosynthetic proinsulin (HPro) were studied in primary cultures of rat hepatocytes. HPro had 3% (on a molar basis) of the potency of porcine insulin for displacing (125I)-TyrA14-insulin from receptors. Maximally effective concentrations of insulin and HPro caused similar stimulations of 14C-glucose incorporation into glycogen and glycogen synthase activity. However, the dose response curve for HPro stimulation of glycogen synthase was shifted far to the right (EC50 = 4.1 +/- 1.1 nM) of that for insulin (.09 +/- .01). The relative biologic potency of HPro was approximately 3%. Biologically equivalent maximal doses of insulin (8.3 nM) and HPro (53.2 nM) stimulated glycogen synthase activity with similar time courses; half maximal between 15-30 min with maximal effects at 60 min. Deactivation of glycogen synthase upon removal of the hormone was very rapid for both hormones. The relative binding and biologic potencies of HPro compared to insulin in liver (approximately 3%) were similar to values previously seen in adipocytes. This fact, together with the similarity of kinetics of action, suggest that the in vivo hepatoselectivity of HPro is not a property of the target cell itself.
在大鼠肝细胞原代培养物中研究了人生物合成胰岛素原（HPro）的结合、生物活性以及作用动力学。HPro在从受体上置换（125I）-酪氨酸A14胰岛素方面，其效力为猪胰岛素的3%（以摩尔计）。胰岛素和HPro的最大有效浓度对14C-葡萄糖掺入糖原和糖原合酶活性的刺激作用相似。然而，HPro刺激糖原合酶的剂量反应曲线比胰岛素的曲线向右大幅偏移（HPro的EC50 = 4.1 +/- 1.1 nM，胰岛素的为0.09 +/- 0.01）。HPro的相对生物活性约为3%。生物学等效的最大剂量胰岛素（8.3 nM）和HPro（53.2 nM）刺激糖原合酶活性的时间进程相似；在15 - 30分钟达到最大效应的一半，60分钟时达到最大效应。去除激素后，两种激素使糖原合酶失活的速度都很快。与胰岛素相比，HPro在肝脏中的相对结合和生物活性（约3%）与之前在脂肪细胞中观察到的值相似。这一事实，连同作用动力学的相似性，表明HPro在体内的肝选择性不是靶细胞本身的特性。
