This investigation was undertaken to study the effect of adrenaline and insulin on the activity of lipid metabolising enzymes in the perfused rat heart. The results demonstrated that adrenaline increased HSL and decreased both LPL and GPAT activities. All these enzyme activities were found to change under conditions consistent with their being capable of being phosphorylated and dephosphorylated by endogenous cAMP dependent kinase and by Mg++/Ca++ dependent phosphoprotein phosphatase respectively. It is believed that such a mechanism is the simplest interpretation of the adrenaline effects found in heart from normal fed animals. In starved animals, HSL activity was increased and this could be further increased by the addition of adrenaline. By contrast, starvation decreased both LPL and GPAT activities. They could be further decreased by treatment with adrenaline. Again the enzyme activities changed under conditions that suggest they were capable of being phosphorylated and dephosphorylated by endogenous cAMP dependent protein kinase and by Mg++ /Ca++ dependent phosphoprotein phosphatase. Both insulin and oleate in hearts from starved animals had inhibitory effects on HSL activity and stimulatory effects on both LPL and GPAT activities. Adrenaline in these conditions and in contrast to earlier results in normal hearts inhibited HSL and stimulated LPL and GPAT activities. These results are not consistent with insulin and oleate altering in the activity of protein kinase and/or phosphoprotein phosphatase. The mechanism for these effects are not known. Since cAMP concentration in cells is not reduced by insulin or oleate and since [cAMP] increases with adrenaline to the normal extent, mechanisms for insulin and oleate action involving an inhibition of adenylate cyclase or stimulation of phosphodiesterase cannot explain these results. The effects of insulin and oleate are consistent with their causing either an inhibition of cAMP dependent protein kinase or a stimulation of Mg++/Ca++ dependent phosphoprotein phosphatase. The results obtained by adrenaline treatment subsequent to either insulin or oleate treatment are not understood. If insulin acts to stimulate a Ca++ dependent phosphoprotein phosphatase and if adrenaline occasions a further increased Ca++ influx then a further stimulation of the phosphoprotein phosphatase could occur.
|Date of Award||1982|