Metabolism of Insulin-I131 Studies in Isolated, Perfused Rat Liver and Hind-limb Preparations
Metabolism of Insulin-I131 Studies in Isolated, Perfused Rat Liver and Hind-limb Preparations
复制标题
离体灌注大鼠肝脏和后肢制剂中胰岛素 I131 的代谢研究
作者：
G. E. Mortimore;F. Tietze;D. Stetten
胰岛素与哺乳动物组织的切片、匀浆或提取物孵育，已被证明会导致其生物失活和蛋白质降解。由于肝脏粗提物对胰岛素有一定的特异性，有人提出可能存在一种特殊的胰岛素降解系统，称为米尔斯基“胰岛素酶”，尽管可检测到的胰岛素蛋白酶水平广泛分布，但在肝脏匀浆中的浓度最高，在肾脏中的浓度相对较小。肌肉是胰岛素的主要靶标，其提取物中似乎只有很少的这种活性。在完整的动物体内，胰岛素的快速破坏可能归因于肝脏和肾脏的活动。然而，这种假设的前提是循环中的胰岛素可以接触到肝和肾脏的细胞内蛋白水解酶，并且“胰岛素酶”活性不是切片和均质制剂的产物。由于所有内源性产生的胰岛素在到达骨骼肌和其他靶器官之前都必须通过肝脏，因此这一途径的后果是相当有趣的。
The incubation of insulin with slices, homogenates or extracts of mammalian tissues has been shown to result in its biological inactivation and proteolytic degradation." Inasmuch as crude extracts of liver have shown some specificity for insulin, the view that a specific insulin degrading system, termed by Mirsky "insulinase," may exist has been proposed/ Although detectable levels of insulin protease are widely distributed, the greatest concentrations are found in homogenates of liver and to a somewhat lesser extent in kidney. Muscle, a prime target of insulin, appears to contain very little of such activity in its extracts. The rapid destruction of insulin in the intact animal could be attributed to hepatic and perhaps renal activity. However, such an assumption presupposes that circulating insulin has access to intracellular proteases of liver and kidney, and that "insulinase" activity is not an artifact of sliced and homogenized preparations. Since all endogenously produced insulin must pass through liver prior to reaching skeletal muscle and other target organs, the consequences of this passage are of considerable interest.