Chloroquine stimulation of insulin binding to IM-9 lymphocytes: Evidence for action at a nonlysosomal site

Chloroquine has been shown to both increase insulin binding and decrease intracellular insulin degradation in several target cells. However, whether this increased binding is a consequence of decreased degradation is unclear. Accordingly, we studied the effects of chloroquine on insulin binding to IM-9 cultured lymphocytes, a cell type that does not degrade insulin in the cell interior. In these cells, chloroquine enhanced insulin binding in a dose dependent manner over the concentration range of 100 μM to 1 mM; at 1 mM binding was increased by 70%. Scatchard analysis indicated that chloroquine acted to increase receptor affinity. These studies indicate, therefore, that chloroquine can enhance the binding of insulin to its receptor via a mechanism that is independent of effects on intracellular insulin degradation.