Differential effects of alcohol upon gluconeogenesis from lactate in young and old hepatocytes

The purpose of this study was to determine the effect of age upon hepatic gluconeogenesis (HGN) from lactate in the presence of various concentrations of alcohol from young (3 months) and old (24 months) male rats. After a 24-hour fast, livers were perfused with collagenase and the hepatocytes were isolated. Aliquots of the cell suspension were placed in Krebs-Henseleit buffer and incubated with lactate, [U-(14)C]lactate, and nine different concentrations of ethanol (EtOH) for 30 min. Dose-effect curves were generated for the determination of maximal and half-maximal alcohol-induced inhibition on gluconeogenesis. There were no significant differences in basal HGN (lactate only and no EtOH) between young and old hepatocytes, 86.9+/-6.3 nmol/mg protein/30 min. The addition of ethanol significantly reduced HGN from lactate in both groups. At the highest ethanol concentration (15 mM), the glucose production was inhibited more from old, 46.1+/-1.2 nmol/mg protein/30 min, compared to young hepatocytes, 56.0+/-1.6 nmol/mg protein/30 min. The greater age-related reduction in HGN was confirmed by the minimal glycogenolysis, and the concomitant decline in [U-(14)C]glucose production, lactate uptake, and [U-(14)C]lactate uptake. The results suggest that alcohol elicits a greater inhibition upon HGN from lactate in old compared to young liver cells.