Regulation of glycogen metabolism in acute uremic hearts.

Abstract

The mechanisms for increased glycogenstores in hearts of acute uremic rats were investigated. The differences in glycogen stores were observed in both fed and fasted animals. Fed uremic rats had higher plasma FFA levels than fed sham-operated animals, but this difference was not seen in the fasting uremic and sham-operated group, suggesting that plasma FFA was not responsible for the elevated cardiac glycogen observed in acute uremia. The recovery of glucose-14C from heart glycogen and the glycogen specific activity were greater in uremic than sham-operated hearts 6 hr after operation, whereas at 24 hr these relationships were reversed. Thus, glycogen synthesis appeared to be stimulated early in the course of uremia, but at 24 hr glycogenesis and glycogenolysis appeared to be depressed in uremic hearts. At 24 hr, glycogen synthetase I activity was found to be decreased and UDPG-glucose elevated in uremic hearts. Phosphorylase a activity was decreased and G-6-P increased in uremic hearts. Uremic hearts responded to epinephrine with greater activation of phosphorylase from the b to the a form. Epinephrine activated myocardial adenyl cyclase in uremic hearts to the same extent as in sham-operated hearts, and cyclic AMP levels did not differ in comparison with sham-operated hearts. With insulin, myocardial UDPG and glycogen content remained higher, and glycogen synthetase I was lower in uremic than sham-operated hearts, although there was partial release of the block at glycogen synthetase step. These studies are consistent with an early increase in glycogenesis followed by a later decrease in glycogenesis and glycogenolysis in acute uremia. Glycogen stores are set at a new high level. A series of factors that influence control of glycogen synthesis and breakdown is altered and may partially explain the new state of glycogen metabolism. The mechanisms for increased glycogenstores in hearts of acute uremic rats were investigated. The differences in glycogen stores were observed in both fed and fasted animals. Fed uremic rats had higher plasma FFA levels than fed sham-operated animals, but this difference was not seen in the fasting uremic and sham-operated group, suggesting that plasma FFA was not responsible for the elevated cardiac glycogen observed in acute uremia. The recovery of glucose-14C from heart glycogen and the glycogen specific activity were greater in uremic than sham-operated hearts 6 hr after operation, whereas at 24 hr these relationships were reversed. Thus, glycogen synthesis appeared to be stimulated early in the course of uremia, but at 24 hr glycogenesis and glycogenolysis appeared to be depressed in uremic hearts. At 24 hr, glycogen synthetase I activity was found to be decreased and UDPG-glucose elevated in uremic hearts. Phosphorylase a activity was decreased and G-6-P increased in uremic hearts. Uremic hearts responded to epinephrine with greater activation of phosphorylase from the b to the a form. Epinephrine activated myocardial adenyl cyclase in uremic hearts to the same extent as in sham-operated hearts, and cyclic AMP levels did not differ in comparison with sham-operated hearts. With insulin, myocardial UDPG and glycogen content remained higher, and glycogen synthetase I was lower in uremic than sham-operated hearts, although there was partial release of the block at glycogen synthetase step. These studies are consistent with an early increase in glycogenesis followed by a later decrease in glycogenesis and glycogenolysis in acute uremia. Glycogen stores are set at a new high level. A series of factors that influence control of glycogen synthesis and breakdown is altered and may partially explain the new state of glycogen metabolism.