Effects of changes in serum insulin in response to dexamethasone and adrenalectomy on insulin-sensitive phosphodiesterase in rat fat cells.

The effects of dexamethasone administration and adrenalectomy on insulin-sensitive phosphodiesterase were studied in rat fat cells. Isolated fat cells were incubated at 37 degrees C for ten minutes or without insulin. A crude microsomal fraction prepared by differential centrifugation was used for the determination of phosphodiesterase level. With dexamethasone treatment (400 micrograms/kg/day) for seven days, specific activity of the enzyme and its sensitivity (ED50) to insulin were decreased, as was the maximal responsiveness to insulin. Under conditions of adrenalectomy, the specific activity and the sensitivity (ED50) were increased while the maximal responsiveness to insulin was decreased. Following dexamethasone treatment specific insulin binding was decreased, and after adrenalectomy it increased. These findings were attributed to changes in the number of insulin receptors per cell rather than to changes in affinity. Alterations in insulin sensitivity (ED50) of the enzyme seemed to be due to alterations in insulin binding to the receptor. The reduction in maximal insulin responsiveness suggested postreceptor defects in both experimental groups. The mechanism related to alterations in the specific activity was not thoroughly clarified; however, serum insulin levels may specifically affect the enzyme activity.