Involvement of Microtubules in Insulin-Receptor Turnover in Cardiac Myocytes

Abstract

The effects of the microtubule- disruptive drug vinblastine on the turnover of cardiac insulin receptors has been studied using isolated muscle cells from adult rat heart. The receptor’s 1/2-life was estimated from the insulin internalization rate to be ~3 h at 10 nM insulin concentration. Increasing the receptor turnover rate resulted in an increasing inhibition of insulin binding after treatment of cells v/ith vinblastine. In the presence of cycloheximide insulin binding decreased by 30%; this effect v/as found to be additive in respect of the action of vinblastine. Treatment of cells with vinblastine significantly reduced the low mol. wt. 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.