J. Wahren

Pathways of hepatic glycogen formation in humans following ingestion of a glucose load in the fed state

The relative contributions of the direct and the indirect pathways to hepatic glycogen formation following a glucose load given to humans four hours after a substantial breakfast have been examined. Glucose loads labeled with [6-(14)C]glucose were given to six healthy volunteers along with diflunisal (1 g) or acetaminophen (1.5 g), drugs excreted in urine as glucuronides. Distribution of 14C in the glucose unit of the glucuronide was taken as a measure of the extent to which glucose was deposited directly in liver glycogen (ie, glucose----glucose-6-phosphate----glycogen) rather than indirectly (ie, glucose----C3-compound----glucose-6-phosphate----glycogen). The maximum contribution to glycogen formation by the direct pathway was estimated to be 77% +/- 4%, which is somewhat higher than previous estimates in humans fasted overnight (65% +/- 1%, P less than 0.05). Thus, the indirect pathway of liver glycogen formation following a glucose load is operative in both the overnight fasted and the fed state, although its contribution may be somewhat less in the fed state.

Quantitation of the pathways followed in the conversion of fructose to glucose in liver

Recently, only about 50% of the conversion of fructose to glucose was reported to be via fructose-1-P aldolase catalysis in children. This was also suggested to be the case in adults. That possibility has been tested using a method that quantifies the pathways of fructose conversion to glucose via the fate of 14C from specifically labeled fructose. Trace [6-14C] fructose or its immediate precursor [6-14C]sorbitol with unlabeled fructose (0.3 mg/kg body weight/min) was given intravenously or intragastrically with trace [1-14C]lactate to six normal adults fasted overnight. The distributions of 14C in glucose from blood samples were determined. The ratios of 14C in C1 to C6 of the glucose were equal to or only slightly less than the ratios of 14C in C3 to C4. Since incorporation into C3 and C4 of glucose must have arisen via the conversion of [1-14C]lactate to [1-14C]triose phosphates, fructose conversion to glucose must also have arisen predominantly via the triose phosphates. From the ratios, 85.1% to 100%, a mean of 94.9% of the fructose converted to glucose is calculated to have been converted to glucose with cleavage of the carbon skeleton of the fructose. These findings contrast with the report that in children under similar conditions only about 50% of the conversion of fructose to glucose is with cleavage. The findings agree with previous results in which fructose was administered to normal adults as a bolus at a dose of 60 mg/kg body weight. The possible reasons that the findings in children are different from those in adults are considered.