Gluconeogenesis in human liver tissue. An in vitro method for evaluation of glyconeogenesis in man

Human liver tissue was obtained as surgical biopsies in 29 subjects operated on for uncomplicated gallstone disease. Liver slices were incubated in Krebs-Ringer bicarbonate buffer solution, pH 7.4, with 17 l-amino acids, lactate, glycerol, and glucose at various concentrations. The incorporation rate of alanine, lactate, and glycerol into glucose, glycogen, and CO2 was determined by use of 14C-labeled precursors. The gluconeogenetic rate of all substrates was increased 10-35 times by increasing precursor concentration in the medium. Insulin at a physiological concentration (300 mU/l) and dexamethasone (0.001 mmol/l) had slight but significant effects on the incorporation rate of alanine into glucose and glycogen, respectively. Glucagon had no effect. Glucose in the incubation medium did not influence the incorporation rate of precursors into glucose, glycogen, or CO2, suggesting that glucose was not of importance for the regulation of the gluconeogenesis. The gluconeogenetic rate of a precursor was not dependent on or influenced by the presence of other precursors. The gluconeogenesis in human liver slices at physiological concentrations of precursors was 5-20% of the maximal rate reported for the rat liver. When the precursor concentration in the medium was increased, the gluconeogenetic rate increased to values close to those reported for the rat liver in vitro and for man in vivo. This in vitro preparation of human liver seems to be valid for evaluation of gluconeogenesis in man.