Decreased insulin responsiveness in fat cells rendered protein kinase C-deficient by a treatment with a phorbol ester.

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 X 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.