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

Department of Biological Sciences, Chapman University, Orange, California 92866

Submitted 6 December 2002 ; accepted in final form 25 April 2003

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; 25,000 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 (V_max and EC₅₀). Maximal Epi-stimulated hepatic glucose production (V_max) 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 V_max 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.

liver; lactate; glucose production; exercise