The mechanism of receptor-mediated degradation of insulin in isolated rat adipocytes: Indirect evidence for a non-lysosomal pathway

Abstract

Receptor-bound insulin is substrate for a degradation leading to the release of about half the cell-associated [ 125I]monoiodoinsulin as [ 125I]monoiodotyrosine. Classical lysosomal inhibitors of the amine type (cloroquine, methylamine and NH +in4) only partly inhibited this receptor-mediated degradation. Leupeptin, which is very effective in other systems, was without any effect in the present system. The degradation could not be reduced by lowering the ATP content of the cells. Sulphydryl reagents strongly inhibited the degradation as has also been shown for the cytosolic insulin-specific protease. Microtubules and microfilaments are probably not involved since inhibitors of the cytoskeleton were without marked effects. It is suggested that in the rat adipocyte only a minor part of the receptor-mediated degradation of insulin takes place via the classical endocytotic lysosomal pathway.