HUMAN KIDNEY AND LIVER GLUCONEOGENESIS - EVIDENCE FOR ORGAN SUBSTRATESELECTIVITY

To assess the contribution of the human kidney to gluconeogenesis (GN) and its role in conversion of glutamine and alanine to glucose, we us ed a combination of isotopic and organ balance techniques in nine norm al postabsorptive volunteers and measured both overall and renal incor poration of these precursors into glucose before and after infusion of epinephrine. In the postabsorptive basal state, renal incorporation o f glutamine (27 +/- 2 mu mol/min) and alanine (2.1 +/- 0.5 mu mol/min) into glucose accounted far 72.8 +/- 3.3 and 3.9 +/- 0.5% of their ove rall incorporation into glucose (37 +/- 2 and 51 +/- 6 mu mol/min, res pectively) and 19.0 +/- 3.5 and 1.4 +/- 0.2%, respectively, of overall renal glucose release. Infusion of epinephrine, which increased syste mic and renal glucose release more than twofold (P < 0.001), increased overall glutamine and alanine incorporation into glucose (both P < 0. 001) and increased renal GN from glutamine (P < 0.001) but not from al anine (P = 0.15). Renal glutamine GN now accounted for 90.3 +/- 4.0% o f overall glutamine GN (P = 0.01 vs. basal), whereas renal alanine GN still accounted for only 4.8 +/- 1.7% of overall alanine GN (P = 0.36 vs. basal). With the assumption that kidney and liver are the only glu coneogenic organs in humans, these results indicate that glutamine GN occurs primarily in kidney, whereas alanine GN occurs almost exclusive ly in liver. Isotopic studies of glutamine and alanine incorporation i nto plasma glucose may provide a selective, noninvasive method to asse ss hepatic and renal GN.