Nonhepatic glucose production in humans.
Level 3 - non-randomized controlled study
Prospective non-randomized comparative study with longitudinal and healthy control comparators
PubMed 12824085 · doi:10.1152/ajpendo.00486.2002
What was done
Extrahepatic glucose kinetics and gluconeogenesis were evaluated during the anhepatic phase of liver transplantation in 14 recipients with localized hepatocarcinoma and mild or absent cirrhosis. Patients received boluses of [6,6-2H2]glucose and L-[3-13C]alanine or L-[1,2-13C2]glutamine. Twelve recipients were evaluated again 7 months later alongside 7 healthy control subjects. The investigators measured renal arteriovenous glucose differences, arterial and portal glucose concentrations, glucose production, clearance, uptake, 13C incorporation into glucose, and circulating gluconeogenic precursor and hormone concentrations.
What was found
During the anhepatic phase, plasma glucose initially rose and then declined by 15%/h. The right kidney released glucose with an arteriovenous gradient of -3.7 mg/dl, while arterial and portal glucose levels were similar. Glucose clearance was reduced by 25%, while glucose uptake was similar to controls. Glucose production was 9.5 +/- 0.9 micromol.kg-1.min-1 (30% less than in controls). Glucose became enriched with 13C from alanine and especially glutamine. Alanine, glutamine, lactate, pyruvate, glycerol, insulin, epinephrine, cortisol, growth hormone, and glucagon were increased severalfold.
Why it matters
This study provides direct in vivo evidence that nonhepatic human organs, primarily the kidney, can sustain substantial gluconeogenesis and glucose release when hepatic function is absent in the presence of elevated substrate and counterregulatory hormone levels.
Limits
The sample size is small (14 surgical patients, 7 controls). The study was conducted during acute surgical hepatectomy with extreme counterregulatory hormone surges, which may not directly generalize to normal basal physiology. Specific non-renal extrahepatic sources could not be definitively isolated or quantified.
Cited by
- supports The primary substrates for gluconeogenesis include lactate, the glycerol backbone of triglycerides, and glucogenic amino acids from diet and skeletal muscle.