Ligand-induced changes in insulin receptors in cell surface and Golgi fractions of fetal rat liver.
The studies described in this paper were undertaken to characterize the insulin receptors present in the plasma membranes and Golgi fractions of fetal rat liver and to determine their subcellular distribution after the administration of exogenous insulin. Purification patterns of both types of liver membranes from fetal and adult rats were similar, as verified by morphological and biochemical approaches. In both groups insulin binding was significantly greater in plasma membranes than in Golgi fractions. However, in plasma membranes insulin binding was similar in both groups, while in Golgi fractions it was greater in fetal than in adult rats, although the difference was not statistically significant. The modifications in insulin binding reflect changes in the number of receptors, but not in the affinity constants. The time courses of insulin association and dissociation from liver membranes were unaffected by development. Degradation of insulin by liver membranes was lower in fetal than in adult rats, although this does not seem to be responsible for the differences observed in binding. No significant differences in the degradation of insulin receptors between different groups of liver membranes were found. The effects of a single injection of insulin on the subcellular distribution of insulin receptors in liver were examined. Insulin administration to adult rats resulted in a marked decrease in insulin binding in liver plasma membranes but a significant increase in Golgi fractions, occurring within 1.5 min. By contrast, in 21-day-old fetuses insulin injection slightly increased insulin binding to liver plasma membranes at 15 min, while in Golgi fractions an increase in insulin binding was only observed 30 min after insulin injection. These findings suggest that the slow ligand-induced translocation of the insulin receptor from the cell surface to Golgi fractions in the fetus might explain the absence of insulin receptor down-regulation in fetal hepatocytes.
de Diego
J G
JG
Departamento de Bioquímica, Facultad de Medicina, Salamanca, Spain.
Blázquez
E
E
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002458:Cell Fractionation; D002462:Cell Membrane / Q000378:metabolism; D005312:Fetal Blood / Q000032:analysis; D006056:Golgi Apparatus / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
D001786:Blood Glucose; D007328:Insulin; D011972:Receptor, Insulin