Effect of age and endurance training on the capacity for epinephrine-stimulated gluconeogenesis in rat hepatocytes.

The effects of endurance training on hepatic glucose production (HGP) from lactate were examined in 24-h-fasted young (4 mo) and old (24 mo) male Fischer 344 rats by using the isolated-hepatocyte technique. The liver cells were incubated for 30 min with 5 mM lactate ([U-14C]lactate; 25000 dpm/ml) and nine different concentrations of epinephrine (Epi). Basal HGP (with lactate only and no Epi) was significantly greater for young trained (T) (99.6 +/- 6.2 nmol/mg protein) compared with young controls (C) (78.2 +/- 6.0 nmol/mg protein). The basal HGP was also significantly greater for old T (97.3 +/- 5.9 nmol/mg protein) compared with old C (72.2 +/- 3.9 nmol/mg protein). After the incubation with the various concentrations of Epi, Hanes-Woolf plots were generated to determine kinetic constants (Vmax and EC50). Maximal Epi-stimulated hepatic glucose production (Vmax) was significantly greater for young T (142.5 +/- 6.5 nmol/mg protein) compared with young C (110.9 +/- 4.8 nmol/mg protein). Similarly, the Vmax was significantly greater for old T (138.2 +/- 5.0 nmol/mg protein) compared with old C (103.9 +/- 2.5 nmol/mg protein). Finally, there was an increase in the EC50 from the hepatocytes of old T (56.2 +/- 6.2 nM) compared with young T (32.6 +/- 4.9 nM). In like manner, there was an increase in the EC50 from the hepatocytes of old C (59.7 +/- 5.8 nM) compared with young C (33.1 +/- 2.7 nM). The results suggest that training elevates HGP in the basal and maximally Epi-stimulated condition, but with age there is a decline in EC50 that is independent of training status.