Gluconeogenesis: methodological approaches in vivo

Abstract

The complexity of the process of gluconeogenesis makes it very difficult to study in vivo. Of the many approaches used to study this process, none have proven ideal. The arterial-hepatic venous catheterization technique can provide accurate determination of the net splanchnic uptake of the various gluconeogenic precursors but gives no information as to their fate once extracted. The infusion of a labeled precursor, such as [14C]alanine, will provide qualitative information about the fate of the labeled substrate but, without complicated kinetic analysis, will not provide quantitative information on the conversion of the precursor to glucose. Though each of these individual techniques has major limitations in the study of gluconeogenesis, various combinations of these methods can provide further insight into the regulation of this complicated process. By combining the arterial-hepatic venous catheterization technique with the infusion of a labeled precursor, the splanchnic extraction of the precursor can be measured as well as the amount of the extracted precursor that is converted to glucose. The concomitant infusion of two isotopes (a 14C-labeled gluconeogenic precursor to assess substrate conversion to glucose and 3H-labeled glucose to measure glucose turnover) can also provide an accurate determination of the amount of circulating precursor that is converted to glucose. The latter technique provides no information on the splanchnic extraction of the precursor but has the advantage of being less invasive and, therefore, more applicable to man. The last two techniques measure accurately the direct conversion of the circulating precursor to glucose and, therefore, provide reliable index of gluconeogenesis.