Correction for the metabolic exchange of 14C for 12C atoms in the pathway of gluconeogenesis in vivo.

Methods designed for estimation of the synthesis of plasma glucose are based on the transfer of 14C atoms from a selected precursor (substrate) such as lactate or alanine. This approach was shown to lead to an underestimation of the true synthesis of glucose because of the metabolic exchange of 14C atoms for 12C atoms in the hepatic oxaloacetate pool. From the incorporation of 14C atoms from intravenously infused [2-14C]acetate into plasma glucose, the extent of the metabolic exchange has been estimated. In normal dogs, metabolic exchange leads to an underestimation of plasma glucose synthesis from plasma lactate or alanine by a factor of 2.2 +/- 0.07, i.e., by 55%. In insulin-deprived diabetic dogs, the factor was found to be 1.8 +/- 0.05. In long-term fasted dogs, the factor may be higher than in the postabsorptive state, whereas treatment with methylprednisolone has no effect. The assumptions and sources of possible errors in the estimation of the extent of metabolic exchange are reviewed.