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Binding and Degradation of Insulin by Isolated Renal Cortical Tubules^*

Nephrology Section, Medical and Research Services, Veterans Administration Wadsworth Medical Center Los Angeles, California 90073;
Endocrinology Section, Department of Medicine, Cedars-Sinai Medical Center Los Angeles, California 90048;
the Department of Medicine, University of California School of Medicine Los Angeles, California 90024

Address all correspondence and requests for reprints to: Kiyoshi Kurokawa, M. D., Nephrology Section, 691/111L, Veterans Administration Wadsworth Medical Center, Los Angeles, California 90073.

Abstract

Binding and degradation of monoiodinated [¹²⁵I]insulin by isolated tubules of rat kidney cortex were studied. Binding and degradation of insulin were dependent on temperature and duration of incubation as well as on the tubule concentration. Degradation was minimized by the use of low to moderate tubule concentrations and an incubation temperature of 22 C. Increasing concentrations of unlabeled insulin (0.1–1000 nM added in the incubation medium) decreased [¹²⁵I]insulin binding in a dose-dependent fashion. Analysis of the data was consistent either with receptors with different affinities or with a single class of receptors, which demonstrates negative cooperativity. Parathyroid hormone and other peptide hormones did not affect [¹²⁵I]insulin binding to tubules. Approximately 70–75% of bound [¹²⁵I]insulin could be dissociated by the subsequent addition of excess unlabeled insulin. Insulin binding preceded degradation, and preincubation of tubules with trypsin abolished binding and degradation of insulin. These data indicate the presence of specific insulin receptors in renal cortical tubules and suggest that binding of insulin to its receptors may be important for insulin degradation. The interaction between insulin binding and degradation may underlie some physiological effects of insulin on renal function and may play a role in the renal metabolism of insulin. (Endocrinology 106: 655, 1980)

Footnotes

^* Portions of the study were published in an abstract form in Clinical Research (26: 159A, 1978) and presented at the Annual Meeting of the American Diabetes Association, Boston, MA, June 1978, and at the Seventh International Congress of Nephrology, Montreal, Canada,June 1978. This work was supported by Veterans Administration and in part by grants from the USPHS (AM-18657 and AM-21351) and American Diabetes Association, Inc.

Received June 18, 1979.