Fate of [125I]insulin removed from the peritubular circulation of isolated perfused rat kidney

Although there is considerable evidence that insulin is removed from the peritubular circulation of the mammalian kidney, it is unclear whether binding to insulin-specific receptors is involved in this process, whether after peritubular removal the hormone is degraded to small fragments with release into the circulation, or whether it merely undergoes a minor modification with loss of immunoreactivity. We examined the metabolism of [125I]insulin removed from the peritubular circulation of the nonfiltering isolated perfused rat kidney and compared it to that of [125I]insulin metabolized by filtering isolated kidneys and kidney homogenates. The results indicate that after peritubular removal, a small amount of insulin is degraded to form low-molecular-weight products similar to those seen with filtering kidneys and kidney homogenates. However, most of the insulin removed from the peritubular circulation is processed either to nonimmunoreactive products of molecular weight similar to that of insulin or, to a lesser extent, to products of larger molecular weight. Both these products are also formed by filtering kidneys. In the filtering kidney, the products having molecular weight similar to that of insulin probably originate from the peritubular process, because it is unlikely that material of this size could be derived from the filtration-absorption pathway. Of particular note was the finding that [125I]insulin trapped in the peritubular compartment of nonfiltering kidneys was displaced severalfold more effectively by unlabeled insulin than by several peptide hormones (P less than 0.01); the latter were no more effective than vehicle alone. The findings suggest the presence of peritubular insulin-specific receptors.