López S, Desbuquois B, Postel-Vinay M C, Benelli C, Lavau M
INSERM Unité 30, Hôpital des Enfants Malades, Paris, France.
Diabetologia. 1988 Dec;31(12):922-7. doi: 10.1007/BF00265378.
Acute hyperinsulinaemias induced by insulin and stimulants of insulin secretion have been shown to cause a translocation of liver insulin receptors from the cell surface to the intracellular compartment, with little or no change in total receptor number. To determine whether a similar phenomenon occurs in chronic hyperinsulinaemic states, we have carried out a longitudinal study of total, cell surface and intracellular liver insulin receptors in genetically obese Zucker rats, with spontaneously develop hyperinsulinaemia. Liver plasma membranes, Golgi-endosomal fractions, a microsomal fraction and a total particulate fraction were isolated in 2-14-week old obese (fa/fa) rats and examined for specific insulin binding relative to lean (Fa/?) age-matched animals. In 16-day old rats, which were still normoinsulinaemic, insulin binding was unchanged. Later on, as hyperinsulinaemia developed, three sequential changes in insulin binding activity were observed: first, a 25-30% increase in Golgi-endosomal fractions (20 days); then, a 50-60% decrease in Golgi-endosomal fractions (4-5 weeks); and finally, a 50% decrease in plasma membranes (11 weeks), microsomal fraction and total particulate fraction (14 weeks), accompanied by restoration in Golgi-endosomal fractions (8-11 weeks). Unlike insulin receptors, insulin extractable from Golgi-endosomal fractions at 4-5 weeks was unchanged or increased. We conclude that, although an early increase in the endocytosis of liver insulin receptors may occur in hyperinsulinaemic Zucker rats, this mechanism does not account for the later decrease in cell surface receptors observed in these animals.
胰岛素及胰岛素分泌刺激剂所诱发的急性高胰岛素血症已被证实可导致肝脏胰岛素受体从细胞表面转位至细胞内区室，而受体总数几乎没有变化。为了确定在慢性高胰岛素血症状态下是否会出现类似现象，我们对遗传性肥胖的 Zucker 大鼠进行了一项纵向研究，这些大鼠会自发出现高胰岛素血症，研究内容包括肝脏中总的、细胞表面的和细胞内的胰岛素受体情况。在 2 - 14 周龄的肥胖（fa/fa）大鼠中分离出肝细胞膜、高尔基体 - 内体组分、微粒体组分和总颗粒组分，并检测相对于年龄匹配的瘦型（Fa/?）动物的特异性胰岛素结合情况。在仍处于正常胰岛素水平的 16 日龄大鼠中，胰岛素结合情况未发生变化。随后，随着高胰岛素血症的发展，观察到胰岛素结合活性出现了三个连续变化：首先，高尔基体 - 内体组分中胰岛素结合活性增加 25 - 30%（20 日龄）；然后，高尔基体 - 内体组分中胰岛素结合活性降低 50 - 60%（4 - 5 周龄）；最后，质膜（11 周龄）、微粒体组分和总颗粒组分（14 周龄）中胰岛素结合活性降低 50%，同时高尔基体 - 内体组分中的胰岛素结合活性恢复（8 - 11 周龄）。与胰岛素受体不同，在 4 - 5 周龄时从高尔基体 - 内体组分中可提取的胰岛素未发生变化或有所增加。我们得出结论，尽管在高胰岛素血症的 Zucker 大鼠中可能会出现肝脏胰岛素受体早期内吞作用增加的情况，但这种机制并不能解释这些动物后期细胞表面受体减少的现象。
