CONTRIBUTIONS OF GLUCONEOGENESIS TO GLUCOSE-PRODUCTION IN THE FASTED STATE

Healthy subjects ingested (H2O)-H-2 and after 14, 22, and 42 h of fast ing the enrichments of deuterium in the hydrogens bound to carbons 2, 5, and 6 of blood glucose and in body water were determined. The hydro gens bound to the carbons were isolated in formaldehyde which was conv erted to hexamethylenetetramine for assay. Enrichment of the deuterium bound to carbon 5 of glucose to that in water or to carbon 2 directly equals the fraction of glucose formed by gluconeogenesis. The contrib ution of gluconeogenesis to glucose production was 47+/-4% after 14 h, 67+/-4% after 22 h, and 93+/-2% after 42 h of fasting. Glycerol's con version to glucose is included in estimates using the enrichment at ca rbon 5, but not carbon 6. Equilibrations with water of the hydrogens b ound to carbon 3 of pyruvate that become those bound to carbon 6 of gl ucose and of the hydrogen at carbon 2 of glucose produced via glycogen olysis are estimated from the enrichments to be similar to 80% complet e. Thus, rates of gluconeogenesis can be determined without correction s required in other tracer methodologies. After an overnight fast gluc oneogenesis accounts for similar to 50% and after 42 h of fasting for almost all of glucose production in healthy subjects.