Cell culture studies of a patient with congenital lipoatrophic diabetes—Normal insulin binding with alterations in intracellular glucose metabolism and insulin action

Abstract

Insulin binding and the action of insulin on several aspects of glucose metabolism have been investigated in cultured fibroblasts derived from a patient with congenital lipoatrophic diabetes and compared to cultures from 9 nondiabetic controls. Incorporation of glucose was elevated in the patient's cells at glucose levels above 0.1 mM. When distribution of labelled glucose was examined, cell associated glycogen and acid soluble material were increased, but the greatest increment was in lactate production. Insulin binding, as indicated by maximum specific 125I-insulin binding and concentration of unlabelled insulin for 50% displacement, was normal, although insulin regulation of the insulin receptor was diminished. Insulin stimulation of total glucose incorporation was reduced in cells from the patient. When insulin stimulation of glycogen synthase was measured directly, the response to insulin was also attenuated. On the other hand, insulin stimulation of hexose transport appeared to be unimpaired. The data indicate alterations in both cell glucose metabolism and insulin response which may be related to the observed insulin resistance of this disorder.