Evidence for the indirect utilization of glucose for the synthesis of hepatic glycogen in man

1. This study was designed to test the hypothesis that three-carbon intermediates can be used in the 'indirect' pathway of glycogen synthesis in human liver (i.e. a route additional to the use of glucose by the 'direct' pathway). 2. After an overnight fast, 13 patients were given an infusion of 20% (w/v) glucose before elective abdominal operation. All received a 2.5 g bolus of 2220 kBq of selectively 3H- and 14C-labelled glucose before removal of a 1 g biopsy of liver. 3H and 14C were determined in purified glycogen as well as in glucose and lactate from samples of peripheral blood. 3. The ratio and specific activities of 3H and 14C in glycogen were found to be significantly lower than those in administered glucose. By calculation, 7-74% of glycogen repletion occurred by indirect pathways and not all of this was from the glucose supplied. 4. This study suggests that the operation of a direct pathway in man is not exclusive and that significant repletion of hepatic glycogen occurs by an indirect route.