Many studies have shown that the kidney plays an important role in the metabolism of many proteins and small peptides. To understand insulin handling in the kidney, we examined urinary insulin excretion under several conditions in patients with mutant insulin syndrome (MIS; insulin Wakayama). Urinary excretion of insulin was studied using high-performance liquid chromatography analysis in patients with MIS. In these patients, most of the insulin extracted from a 24-hour urine collection and from urine collected after stimulation of insulin secretion by glucose or glucagon was normal insulin, whereas 90% of serum insulin is structurally abnormal (Leu-A3 insulin). On the other hand, arginine, which is known as an inhibitor of renal tubular reabsorption, increased urinary excretion of Leu-A3 insulin. The ratio of Leu-A3 and normal insulin in urine after arginine was similar to that in serum. A large amount of Leu-A3 insulin is excreted in urine when reabsorption of insulin at renal tubules is inhibited by arginine. These data indicate that normal and Leu-A3 insulin are filtered through the glomerulus with relatively little restriction. Using the fact that basal urine has a high concentration of normal insulin and an extremely low concentration of Leu-A3 insulin, which has less receptor-binding affinity, we speculated some possibilities. One possibility is that both forms of insulin are reabsorbed by the tubular cells, but with different efficiencies. Leu-A3 insulin absorption in more complete, and this suggests differences in the uptake pathways that may account for the differences in response to arginine infusions. Another possibility is that only normal insulin is secreted from tubules into urine which is mediated by receptors. Our results provide new insight into renal metabolism of insulin and showed that MIS is a useful model for studying it.

译文

:许多研究表明,肾脏在许多蛋白质和小肽的代谢中起着重要作用。为了了解肾脏中胰岛素的处理方法,我们在突变胰岛素综合征(MIS;和歌山胰岛素)的患者中检查了几种情况下的尿中胰岛素排泄。使用高效液相色谱分析对MIS患者的尿液中的胰岛素进行了研究。在这些患者中,从24小时尿液收集以及葡萄糖或胰高血糖素刺激胰岛素分泌后收集的尿液中提取的大多数胰岛素是正常胰岛素,而90%的血清胰岛素在结构上是异常的(Leu-A3胰岛素)。另一方面,作为肾小管重吸收抑制剂的精氨酸可增加Leu-A3胰岛素的尿排泄。精氨酸后尿液中Leu-A3和正常胰岛素的比例与血清中的相似。当精氨酸抑制肾小管对胰岛素的重吸收时,尿中会分泌大量Leu-A3胰岛素。这些数据表明正常和Leu-A3胰岛素通过肾小球滤过的情况相对较少。利用基础尿液中高浓度的正常胰岛素和极低浓度的Leu-A3胰岛素(具有较少的受体结合亲和力)这一事实,我们推测了一些可能性。一种可能性是两种形式的胰岛素都被肾小管细胞吸收,但效率不同。 Leu-A3胰岛素吸收更完全,这表明摄取途径的差异可能解释了精氨酸输注反应的差异。另一种可能性是仅正常胰岛素从肾小管分泌到尿液中,这是由受体介导的。我们的结果为胰岛素的肾脏代谢提供了新的见识,并表明MIS是研究胰岛素的有用模型。

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