Se. Joseph et al., Renal glucose production compensates for the liver during the anhepatic phase of liver transplantation, DIABETES, 49(3), 2000, pp. 450-456
The extent of the renal contribution to postabsorptive endogenous glucose p
roduction (EGP) in humans is controversial. We measured EGP in the absence
of the liver during the anhepatic phase (AH) of liver transplantation in fi
ve patients (aged 46.4 +/- 10.2 years, two women). Stable labeling of plasm
a glucose (PG) was achieved for a 2-h period before the AH by primed contin
uous infusion of di-deuterated 6,6[H-2(2)]glucose (1.7 mg/min) and continue
d throughout the AH. PG was maintained above the fasting level (6.1 +/- 2.7
3 mmol/l) with 5% dextrose labeled with 6,6[H-2(2)]glucose throughout the A
H (mean level during the AH 0.98 +/- 0.45 mg . kg(-1) . min(-1)). Isotopic
enrichment remained stable at 0.84 +/- 0.21% atom percent excess throughout
. EGP, calculated by use of a modified Steele equation, decreased from 2.6
+/- 1.24 at baseline to 0.97 +/- 0.9 mg . kg(-1) . min(-1) (36% baseline, P
= 0.045) but recovered at similar to 30 min to reach 1.38 +/- 0.83 mg . kg
(-1) . min(-1) (54% baseline) by 60 min. Epinephrine, lactate, free fatty a
cid, and glycerol levels increased significantly (0.79 +/- 0.74 to 3.65 +/-
2.1 nmol/l, P = 0.005; 1.88 +/- 0.43 to 3.46 +/- 0.9 mmol/l, P = 0.024; 54
3.9 +/- 215.5 to 705.5 +/- 219.2 mu mol/l, P = 0.012; 75.6 +/- 30.2 to 139
+/- 96.3 mu mol/l, P = 0.003, respectively). These data show that postabsor
ptive nonhepatic glucose production in humans may contribute to greater tha
n one-third of overall EGP, increasing when required, and that it is associ
ated with a stress response and increased gluconeogenic substrate availabil
ity. We conclude that extrahepatic tissues, most notably those of the kidne
y, make a significant contribution to EGP in humans.