The renal metabolism of insulin: Urinary insulin excretion in patients with mutant insulin syndrome (insulin Wakayama)

Many studies have shown that the kidney plays an important role in the meta bolism of many proteins and small peptides. To understand insulin handling in the kidney, we examined urinary insulin excretion under several conditio ns in patients with mutant insulin syndrome (MIS; insulin Wakayama). Urinar y excretion of insulin was studied using high-performance liquid chromatogr aphy analysis in patients with MIS. In these patients, most of the insulin extracted from a 24-hour urine collection and from urine collected after st imulation of insulin secretion by glucose or glucagon was normal insulin, w hereas 90% of serum insulin is structurally abnormal (Leu-A3 insulin). On t he other hand, arginine, which is known as an inhibitor of renal tubular re absorption, 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 o f insulin at renal tubules is inhibited by arginine. These data indicate th at normal and Leu-A3 insulin are filtered through the glomerulus with relat ively little restriction. Using the fact that basal urine has a high concen tration of normal insulin and an extremely low concentration of Leu-A3 insu lin, which has less receptor-binding affinity, we speculated some possibili ties. One possibility is that both forms of insulin are reabsorbed by the t ubular cells,but with different efficiencies. Leu-A3 insulin absorption in more complete, and this suggests differences in the uptake pathways that ma y account for the differences in response to arginine infusions. Another po ssibility is that only normal insulin is secreted from tubules into urine w hich is mediated by receptors. Our results provide new insight into renal m etabolism of insulin and showed that MIS is a useful model for studying it. Copyright (C) 2001 by WB, Saunders Company.