Measuring glucose and fructose-6-phosphate cycling in liver in vivo

Approaches measuring futile cycling of glucose and fructose-6-phosphate (fructose-6-P) in liver in vivo depend on assumptions about the fates of hydrogens bound to specific carbons of glucose. Thus, 3H of [2-3H]glucose has been assumed to be completely removed after its conversion to glucose-6-P, [3-3H]glucose after its conversion to fructose-1,6-bisP, and [6-3H]glucose not at all. Previous measurements have shown that these assumptions are incompletely fulfilled. Corrections to estimates of cycling can be made when detritiations of [2-3H]glucose and [3-3H]glucose are not complete, and detritiation of [6-3H]glucose occurs. How the corrections can be made is presented using data previously reported on giving labeled glucoses to humans after an overnight fast and on infusing a glucose load. Estimates of glucose cycling nearly double, and that of fructose-6-P cycling almost triples. Estimates of hepatic glucose production as measured with [6-3H]glucose decrease. Correction of estimates of cycling under other conditions may very well be similarly affected. Thus, rates of glucose and fructose-6-P cycling appear to be substantially more than previously estimated. Quantitation under a given condition requires measurements to be made of the extent to which assumptions as to the fate of labeled hydrogen of the glucoses are fulfilled. The uncertain extent of exchange of label catalyzed by transaldolase and detritiation in the pentose cycle, the failure of fructose-6-P cycling to be expressed through detritiation of 3H from [3-3H]glucose, and possible isotope effects still limit the confidence that can be placed in such estimates.