PROGRESSIVE DECREASE IN TISSUE GLYCOGEN-CONTENT IN RATS WITH LONG-TERM CHOLESTASIS

Liver and skeletal muscle glycogen metabolism were investigated in rat s 1 and 4 weeks after bile duct ligation (BDL) and in pair-fed, sham-o perated control rats. Livers were subjected to morphometric analysis t o express glycogen content and enzyme activities per mt hepatocytes. O ne week after BDL, the hepatic glycogen content was 28.8 +/- 13.8 vers us 38.6 +/- 16.4 mg/mL hepatocyte in BDL and control rats, respectivel y. Total activity of glycogen synthase (50.2 +/- 7.0 vs. 63.5 +/- 9.4 mU/mL hepatocytes) and glycogen phosphorylase (59.4 +/- 12.9 vs. 90.8 +/- 18.9 U/mL) were significantly reduced in BDL whereas the active fr action of glycogen synthase (27 +/- 6 vs. 38 +/- 5%) but not of glycog en phosphorylase was reduced. The skeletal muscle glycogen content was not different between BDL and control rats. Four weeks after BDL, hep atic glycogen content was further reduced (20.5 +/- 14.2 vs. 52.9 +/- 6.4 mg/mL). Total activity of glycogen synthase (38.8 +/- 12.1 vs. 60. 1 +/- 4.6 mU/mL hepatocytes) and glycogen phosphorylase (127 +/- 19 vs . 178 +/- 33 U/mL hepatocytes) were both reduced in BDL rats as were t heir corresponding active fractions (30 +/- 18 vs. 66 +/- 8% and 58 +/ - 10 vs. 76 +/- 10). At this time point, the glycogen content in soleu s muscle was decreased by 64% in BDL. The glucagon plasma concentratio n was increased in BDL rats at both time points. There were positive c orrelations between the volume fraction and both hepatic glycogen cont ent and total activity of hepatic glycogen synthase. Plasma glucagon a nd the active fraction of hepatic glycogen synthase were negatively co rrelated. The current studies show a progressive decrease in the hepat ic and skeletal muscle glycogen content in BDL rats. The observed decr ease in the activities of glycogen synthase and phosphorylase suggest that reduced glycogen synthesis is the major mechanism leading to the reduction in the hepatic glycogen content in BDL rats.