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Isolated muscle cells from adult rat heart have been used to study the effects of microtubule disruptive drugs on the maintenance of steady-state insulin binding to cardiac insulin receptors. Vinblastine, vincristine and podophyllotoxin significantly inhibited insulin binding (25-50%) in the presence of insulin (10(-8) mol/l). The effect of vinblastine was found to be time- and temperature-dependent and to be dependent on the amount of insulin bound to the cell. In the presence of cycloheximide (0.1 mmol/l) insulin binding decreased by 30%; this effect was found to be additive to the action of vinblastine. Treatment of cells with vinblastine significantly reduced the low-molecular mass material produced by receptor-mediated degradation of insulin. This effect was not additive to that of the lysosomotropic agent chloroquine. The results suggest involvement of microtubules in the intracellular transfer of insulin receptors from and to the plasma membrane.

Effects of Microtubule-Disrupting Agents on Insulin Binding and Degradation in Isolated Cardiocytes from Adult Rat