USE OF (H2O)-H-2 FOR ESTIMATING RATES OF GLUCONEOGENESIS - APPLICATION TO THE FASTED STATE

A method is introduced for estimating the contribution of gluconeogene sis to glucose production. (H2O)-H-2 is administered orally to achieve 0.5% deuterium enrichment in body water, Enrichments are determined i n the hydrogens bound to carbons 2 and 6 of blood glucose and in urina ry water, Enrichment at carbon 6 of glucose is assayed in hexamethylen etetramine, formed from formaldehyde produced by periodate oxidation o f the glucose. Enrichment at carbon 2 is assayed in lactate formed by enzymatic transfer of the hydrogen from glucose via sorbitol to pyruva te, The fraction gluconeogenesis contributes to glucose production equ als the ratio of the enrichment at carbon 6 to that at carbon 2 or in urinary water. Applying the method, the contribution of gluconeogenesi s in healthy subjects was 23-42% after fasting 14 h, increasing to 59- 84% after fasting 42 h. Enrichment at carbon 2 to that in urinary wate r was 1.12+/-0.13. Therefore, the assumption that hydrogen equilibrate d during hexose-6-P isomerization was fulfilled. The H-3/C-14 ratio in glucose formed from [3-H-3,3-C-14]lactate given to healthy subjects w as 0.1 to 0.2 of that in the lactate. Therefore equilibration during g luconeogenesis of the hydrogen bound to carbon 6 with that in body wat er was 80-90% complete, so that gluconeogenesis is underestimated by 1 0-20%. Glycerol's contribution to gluconeogenesis is not included in t hese estimates. The method is applicable to studies in humans of gluco neogenesis at safe doses of (H2O)-H-2.