Assessment of postabsorptive renal glucose metabolism in humans with multiple glucose tracers

The contribution of the kidneys to postabsorptive endogenous glucose produc tion is a matter of controversy. To assess whether this could relate to the use of various isotopical methods with different analytical performance ca pabilities, we measured glucose kinetics in 12 healthy subjects. Blood samp les were taken from the femoral artery and the renal vein after 4 h of [B,6 -H-2(2)]glucose infusion (for gas chromatography [GC]/mass spectrometry [MS I analysis), and renal plasma flow was determined with paraaminohippurate. In addition, six subjects received uniformly labeled [C-13]glucose (for GC/ combustion/isotope ratio MS [IRMS]) and [3-H-3]glucose (for counting of rad ioactive disintegrations). Arterial glucose concentrations (means +/- SD) w ere 4.2 +/- 0.1 mmol/l, and endogenous glucose production rates using [H-2( 2)]glucose were 2.2 +/- 0.1 mg . kg(-1) . min(-1) or 818 +/- 50 mu mol/min. Dilution of [H-2(2)]glucose across the kidney was 0.79 +/- 1.32%, and rena l glucose production (RGP) rates were 27 +/- 72 mu mol/min. In the six subj ects receiving additional tracers, dilutions across the kidney were 2.83 +/ - 0.72 and 0.54 +/- 1.20 (for [U-C-13]glucose and [3-H-3]glucose, respectiv ely, the dilution with [U-C-13] being higher than that with [H-2(2)] (P = 0 .007). Corresponding BGP values were 144 +/- 39 and 43 +/- 76 mu mol/l min for [U-C-13] and [3-H-3], respectively In conclusion, we found that the hig hly sensitive [U-C-13] GC/Combustion/IRMS technique showed consistent dilut ion of label across the kidney, whereas the less sensitive techniques gave some negative values and smaller RGP rates. Thus, depending on which techni que is being used, a fivefold difference in calculated RGP values may be en countered. The methodological variability of our data suggests that extrapo lation from regional renal measurements to the whale-body level should be p erfumed with caution.