Ultrastructural basis for chloroquine-induced increase in intracellular insulin in adipocytes: alteration of lysosomal function.
A quantitative morphological analysis of insulin uptake into adipocytes was undertaken to determine the structural basis for chloroquine-induced increases in intracellular insulin. Adipocytes were incubated with ferritin-labeled insulin in the presence or absence of 50 microM chloroquine at 37 degrees C for 2-90 min and the uptake of the hormone conjugate was determined quantitatively. Quantitative morphometry of cellular organelles also was performed. Chloroquine treatment of adipocytes incubated with 70 nM ferritin-labeled insulin resulted in: (i) a 120% increase in the number of lysosomes in the cytoplasm; (ii) a 75% increase in the average concentration of ferritin-labeled insulin in a lysosome; and (iii) a 25% increase in the percentage of lysosomes containing ferritin-labeled insulin. The cumulative result of these effects was a substantial increase in the amount of intact intracellular hormone within the lysosomes. These morphological data are consistent with biochemical data concerning chloroquine-induced accumulation of 125I-labeled insulin in adipocytes.
D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002451:Cell Compartmentation; D002738:Chloroquine / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D007425:Intracellular Membranes / Q000648:ultrastructure; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D011480:Protease Inhibitors; D051381:Rats; D011972:Receptor, Insulin / Q000187:drug effects
D007328:Insulin; D011480:Protease Inhibitors; D002738:Chloroquine; D011972:Receptor, Insulin