Effect of prolonged uremia on insulin metabolism by isolated liver and muscle.
Effect of prolonged uremia on insulin metabolism by isolated liver and muscle.
复制标题
长期尿毒症对离体肝脏和肌肉胰岛素代谢的影响。
作者：
R. Rabkin;S. Unterhalter;W. Duckworth
由于慢性尿毒症患者胰岛素代谢清除率延长不能完全由肾脏对胰岛素的清除和降解受损来解释，我们着手确定长期尿毒症是否抑制了胰岛素降解的其他主要部位。本研究采用正常对照大鼠和80%肾切除后4周的尿毒症大鼠的肝脏和骨骼肌进行。尽管对照和尿毒症大鼠的肾功能之间存在显著差异（BUN，18与46 mg/dl），但用无血培养基灌注的离体尿毒症或对照肝脏的胰岛素清除率无显著差异。同样，肝匀浆的125 I-胰岛素降解活性不受尿毒症的抑制。相反，尿毒症肝细胞膜的结合和降解分别显著降低至对照组的58%和85%。降解骨骼肌匀浆和完整的epitrochlaris肌肉是显着低于在尿素氮控制。这些结果表明，慢性尿毒症抑制骨骼肌胰岛素降解，但不肝胰岛素清除或降解，尽管减少胰岛素结合和降解肝质膜。因此，似乎肌肉对胰岛素降解的抑制可能有助于慢性尿毒症中观察到的胰岛素代谢清除率延长。此外，胰岛素与肝细胞膜的结合受损可能在尿毒症的胰岛素抵抗中起作用。
As the prolonged metabolic clearance rate of insulin in chronic uremia cannot be entirely explained by impaired removal and degradation of insulin by the kidney, we set out to determine whether prolonged uremia depresses other major sites of insulin degradation. The study was conducted with livers and skeletal muscle obtained from normal control rats and uremic rats 4 weeks after 80% nephrectomy. Despite a significant difference between renal function in the control and uremic rats (BUN, 18 vs. 46 mg/dl), there was no significant difference in the clearance of insulin by isolated uremic or control livers perfused with a bloodless medium. Similarly, the 125I-insulin degrading activity of liver homogenates was not depressed by uremia. In contrast, binding and degradation by uremic liver cell membranes was significantly reduced to 58% and 85% of the controls, respectively. Degradation by homogenates of skeletal muscle and by intact epitrochlaris muscle was significantly less in uremics than in controls. These results indicate that chronic uremia depresses skeletal muscle insulin degradation but not hepatic insulin removal or degradation despite a decrease in insulin binding and degradation by liver plasma membranes. It thus appears that depression of insulin degradation by muscle may contribute to the prolonged insulin metabolic clearance rate seen in chronic uremia. Furthermore, it is possible that the impaired binding of insulin to liver membranes may play a role in the insulin resistance of uremia.