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Receptor-Mediated Endocytosis of Polypeptide Hormones Is a Regulated Process: Inhibition of [¹²⁵I]Iodoinsulin Internalization in Hypoinsulinemic Diabetes of Rat and Man^*

Institute of Histology and Embryology, University of Geneva School of Medicine Geneva, Switzerland
Institut National de la Sante et de la Recherche Medicale (INSERM U-145) Nice, France
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases, National Institutes of Health Bethesda, Maryland 20892

Address requests for reprints to: Dr. Jean-Louis Carpentier, Institute of Histology and Embryology, CMU, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.

Much data suggest that receptor-mediated endocytosis is regulated in states of hormone excess. Thus, in hyperinsulinemic states there is an accelerated loss of cell surface insulin receptors. In the present experiments we addressed this question in hypoinsulinemic states, in which insulin binding to cell surface receptors is generally increased. In hepatocytes obtained from hypoinsulinemic streptozotocin-induced diabetic rats, [¹²⁵I]iodoglucagon internalization was increased, while at the same time [¹²⁵I]iodoinsulin internalization was decreased. The defect in [¹²⁵I]iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of [¹²⁵I]iodoinsulin was impaired; this defect was not present in insulin-treated patients. These data in the hypoinsulinemic rat and human diabetes suggest that receptor-mediated endocytosis is regulated in states of insulin deficiency as well as insulin excess. Delayed or reduced internalization of the insulin-receptor complex could amplify the muted signal caused by deficient hormone secretion.

^* Portions of these data have been presented in abstract form (1). This work was supported by Grant 3.460.83 from the Swiss National Science Foundation.

Received December 16, 1985.

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