Diabetes, Vol 34, Issue 10 1025-1030, Copyright © 1985 by American Diabetes Association

ARTICLES

Insulin and insulin receptor uptake into rat liver. Chloroquine action on receptor recycling

MN Khan, S Savoie, RJ Khan, JJ Bergeron and BI Posner

In the present study, the effect of chloroquine on both insulin and receptor distribution was examined in vivo. Insulin injection (25 nmol/100 g body wt) caused a marked accumulation of both insulin and its receptor in purified hepatic Golgi fractions by 15 min postinjection. Percoll fractionation of parent Golgi fractions resolved two endocytic components of low (rho = 1.040-1.050) and high (rho = 1.053-1.064) density in which the relative distribution of insulin binding sites was unaltered by chloroquine. Chloroquine significantly accumulated in the high-density region of the Percoll gradient consistent with this being a low pH compartment. 125I-insulin accumulated first in the low-density (1 min) and subsequently in the high-density region (5-10 min) of Percoll-subfractionated Golgi fractions. Chloroquine treatment caused marked accumulation of 125I-insulin in the high-density compartment with substantial retention of radiolabel therein at 20 min postinjection. 125I-insulin extracted from the Percoll fractions was comparably intact in control and chloroquine-treated rats. These data suggest that the chloroquine-accumulating, high-density compartment of hepatic Golgi fractions is the site of dissociation of internalized insulin-receptor complexes before degradation of the ligand and receptor recycling.
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