Limitations in the use of [U-13C6]glucose to estimate gluconeogenesis.

THE EFFORTS of Drs. J. Kelleher, W.-N. P. Lee, and J. Radziuk to resolve the differences between our formulas and those of Drs. J. A. Tayek and J. Katz are greatly appreciated. However, with deep regret and due respect for Drs. Radziuk and Lee, they (26) misinterpret the contributions of my colleagues and myself (21). We have never proposed a method for measuring rates of gluconeogenesis using [U-C6]glucose. Tayek and Katz proposed such a method that, applied under fasting conditions, resulted in physiologically reasonable estimates (13, 30). However, their estimates were based on a theoretically unsound equation, which we corrected. Then we showed using our equation that their method gave ‘‘impossibly low’’ estimates. It is incorrect to interpret that to mean we proposed a method that was the same as that of Tayek and Katz, except for use of an equation that we knew gave impossibly low estimates. There is only one method using [U-C6]glucose under discussion, that of Tayek and Katz. Conclusions given by Radziuk and Lee in their abstract (26) are what we concluded with regard to the proposed method of Tayek and Katz, but those conclusions should not be extended to a method we never proposed. Because Radziuk and Lee recognize the need to correct the equations of Tayek and Katz, as we did, they conclude, as we did, that the method gives estimates lower than physiologically expected. The only difference between their conclusions and ours is that they conclude that assumptions made by Tayek and Katz may not hold, and we conclude that they do not hold. We hope no one uses our equation to estimate rates of gluconeogenesis (28). If they do, the estimates will be impossibly low (21). The equations of Tayek and Katz to calculate the fractional contribution of gluconeogenesis lack a required factor of 0.5. Our equation (21) and the equations of Tayek and Katz [corrected and with the introduction of the molecular formulation (15)] are best expressed as