Modulation of insulin action by fasting: a study using a phosphodiesterase activation system in rat fat cells

Fat cells from control and 72 h fasted rats were incubated with increasing concentrations of insulin at 37 degrees C for 10 min. A crude microsomal fraction from these cells was used for the determination of phosphodiesterase activity. Specific activities of the enzyme in fat cells from the fasted rats were higher at overall insulin concentrations. In the fasted rats the curve shifted to the left at the lower concentrations of insulin and the half-maximal dose was lower than in the controls. Specific binding of insulin to the receptor was increased at the lower concentrations of insulin in fat cells from the fasted rats and Scatchard analysis of the data revealed that the change was due to an increase in binding affinity rather than that in receptor number per cell. Therefore, it is feasible that there is a good correlation with alteration of insulin sensitivity and insulin binding. The net amount of maximal response to insulin assessed as enzyme activity per cell was markedly decreased with fasting, however, this seems to be due to a decrease in absolute amount of the enzyme per cell. Since the maximal activation of the enzyme expressed as a percent of the basal remained unchanged, the steps between insulin receptor and the phosphodiesterase may not be altered under these conditions.