DECREASED INSULIN RESPONSIVENESS IN FAT CELLS RENDERED PROTEIN KINASE C-DEFICIENT BY A TREATMENT WITH A PHORBOL ESTER.

Abstract
Insulin stimulation of 2-deoxyglucose transport and lipogenesis from glucose was examined in fat cells in which protein kinase C had been down-modulated by a 3 h pretreatment with 5 .times. 10-7 M 4.beta.-phorbol 12.beta.-myristate, 13.alpha.-acetate (PMA). As compared to control fat cells, the down-modulated cells exhibited a 55-65% decrease in insulin responsiveness with no change in either the hormone sensitivity or the insulin receptor affinity. The present study shows that fat cells made protein kinase C-deficient by chronic treatment with PMA exhibit an insulin-resistant state, distal to the initial step of hormone binding.