LIMITATIONS IN ESTIMATING GLUCONEOGENESIS AND CORI CYCLING FROM MASS ISOTOPOMER DISTRIBUTIONS USING [U-C-13(6)]GLUCOSE

Tayek and Katz proposed calculating gluconeogenesis's contributions to glucose production and Cori cycling from mass isotopomer distribution s in blood glucose and lactate during [U-C-13(6)]glucose infusion [Tay ek, J. A., and J. Katz. Am. J. Physiol. 272 (Endocrinol. Metab. 35). E 416-E484, 1997]. However, isotopic exchange was not adequately differe ntiated from dilution, nor was condensation of labeled with unlabeled triose phosphates properly equated. We introduce and apply corrected e quations to data from subjects fasted for 12 and 60 h. Impossibly low contributions of gluconeogenesis to glucose production at 60 h are obt ained (23-41%). Distributions in overnight-fasted normal subjects calc ulate to only similar to 18%. Cori cycling estimates are similar to 10 -15% after overnight fasting and 20% after 60 h of fasting. There are several possible reasons for the underestimates. The contribution of g luconeogenesis is underestimated because glucose production from glyce rol and amino acids not metabolized via pyruvate is ascribed to glycog enolysis. Labeled oxaloacetate and alpha-ketoglutarate can exchange du ring equilibrium with circulating unlabeled aspartate, glutamate, and glutamine. Also, the assumption that isotopomer distributions in arter ial lactate and hepatic pyruvate are the same may not be fulfilled.