Abstract
The mechanism of stimulation of glycogen synthesis by fructose was examined in perfused rat livers by application of a newly developed glycogen synthase assay method that measures UDP formation by high-performance liquid chromatography. In a liver perfused with 10mM glucose, glycogen accumulated at 0.10μmol glucosyl units/min/g, 13% of the rate in livers of refed rats. With 20mM glucose, the rate was 0.18μmol glucosyl units/min/g, and without glucose, glycogen decreased at a rate of 0.02μmol glucosyl units/min/g. With the addition of 2mM fructose to the perfusate, the rate was increased to 0.12, 0.34, and 0.54μmol glucosyl units/min/g at glucose concentrations of 0, 10, and 20mM, respectively. Thus, at the higher concentration of glucose, the larger increase of glycogen synthesis by fructose was observed. Similar phenomena were also observed in the changes of the activity of glycogen synthase and glucose 6-phosphate (glucose 6-P) level by fructose administration. Based on the good correlations observed between the rate of glycogen synthesis, % a form of glycogen synthase, and cellular glucose 6-P level, we conclude that stimulation of glycogen synthesis by fructose was due to activation of glycogen synthase, which in turn was brought about by the increase in glucose 6-P level. The increase in glucose 6-P level by fructose loading is thought to be due to not only increased supply of glucose 6-P but also inhibition of microsomal glucose 6-phosphatase by fructose 1-phosphate.
