Internalization of the neonatal brain insulin receptor.
Using 10-15 day neonatal rabbit brain cells, we studied the internalization (n = 6) and intracellular degradation (n = 8) of specifically bound 125I-insulin. In addition we investigated the association between the internalization of the specifically bound 125I-insulin and the metabolic effects of insulin such as glucose (n = 13) and amino-acid (leucine) uptake (n = 6). Phenylarsine oxide (10 microM), an agent that inhibits the internalization of the insulin receptor (n = 6) decreased the specifically bound 125I-insulin in the intact and trypsin-resistant (inside) part of the brain cells by 50% (p less than 0.05). On the other hand chloroquine (100 microM), a lysosomotropic agent that interferes with the intracellular degradation of the insulin receptor (n = 8) increased two-fold the 125I-insulin specifically bound to the intact and trypsin resistant part of the cells (p less than 0.05). Both these agents did not alter the time-dependent basal glucose uptake by the brain cells. Glucose alone regulated its own uptake (n = 4) whereas 1 X 10(-6) M insulin did not augment the glucose uptake (n = 11+13) above basal. Similarly leucine regulated the leucine uptake (n = 4) but insulin did not alter this basal uptake by the brain cells (n = 6). In summary we observed no associated glucose or leucine uptake along with the presence of internalization and intracellular degradation of specifically bound 125I-insulin in the brain cells.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001152:Arsenicals / Q000494:pharmacology; D001923:Brain Chemistry; D002738:Chloroquine / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D066298:In Vitro Techniques; D007930:Leucine / Q000378:metabolism; D011817:Rabbits; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D000596:Amino Acids; D001152:Arsenicals; C029341:oxophenylarsine; D002738:Chloroquine; D003847:Deoxyglucose; D011972:Receptor, Insulin; D007930:Leucine