Receptor-mediated endocytosis of polypeptide hormones is a regulated process: inhibition of (125I)iodoinsulin internalization in hypoinsulinemic diabetes of rat and man
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, (/sup 125/I)iodoglucagon internalization was increased, while at the same time (/sup 125/I)iodoinsulin internalization was decreased. The defect in (/sup 125/I)iodoinsulin internalization was corrected by insulin treatment of the animal. In peripheral blood monocytes from patients with type I insulinopenic diabetes, internalization of (/sup 125/I)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.
- Research Organization:
- Univ. of Geneva School of Medicine, Switzerland
- OSTI ID:
- 5269670
- Journal Information:
- J. Clin. Endocrinol. Metab.; (United States), Vol. 1
- Country of Publication:
- United States
- Language:
- English
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DIABETES MELLITUS
PATHOGENESIS
INSULIN
RECEPTORS
UPTAKE
AUTORADIOGRAPHY
GLUCAGON
IN VITRO
INHIBITION
IODINE 125
LABELLED COMPOUNDS
LIVER
LIVER CELLS
RATS
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BODY
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
ENDOCRINE DISEASES
GLANDS
HORMONES
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
MAMMALS
MEMBRANE PROTEINS
METABOLIC DISEASES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PEPTIDES
POLYPEPTIDES
PROTEINS
RADIOISOTOPES
RODENTS
SOMATIC CELLS
VERTEBRATES
551001* - Physiological Systems- Tracer Techniques