ROLE OF NOREPINEPHRINE IN HEPATIC GLUCONEOGENESIS - EVIDENCE OF AGINGAND TRAINING EFFECTS

This study examined the relationship among the sympathetic neurotransm itter norepinephrine (NE), hepatic gluconeogenesis, and glyconeogenesi s in 63 (30 trained and 33 untrained) young (7 mo), middle-aged (15 mo ), and old (25 mo) male Fischer 344 rats. Animals were trained 1 h/day , 5 days/wk for 10 wk at treadmill speeds of 75% of age-specific maxim al capacity. Liver sections, removed at rest, were sliced and incubate d in [C-14]lactic acid and 0, 0.5, 1.0, 3.0, or 6.0 ng/ml NE, The rate of [C-14]lactate incorporation into glucose was significantly greater in young compared with old animals in both training groups and at all NE concentrations. All trained animals had greater rates of glucose p roduction from lactate than their untrained counterparts at 0.5, 1.0, 3.0, and 6.0 ng/ml NE. At each NE concentration, the old rats showed t he lowest rates of glycogen synthesis from lactate. The untrained rats in all age groups were the least responsive to increases in NE concen tration. Total hepatic glycogen synthase activity exhibited age-relate d declines as the young and middle-aged had significantly greater tota l activity compared with the old animals: 620.4 +/- 27.5, 590.0 +/- 37 .9, and 436.3 +/- 44.5 disintegrations/min, respectively. No differenc es with training were found in total activity. The percent of glycogen synthase in the active form was significantly greater in young compar ed with old in both the trained (48.6 +/- 2.0 vs. 40.0 +/- 1.3% active ) and untrained animals (44.7 +/- 2.2 vs. 35.4 +/- 1.5% active). Phosp hoenolpyruvate carboxykinase activity declined with age as the old ani mals in both training groups had significantly lower activity compared with the young animals (decreased 42 and 59% in the trained and untra ined, respectively). No significant differences in activity existed wi th training. These data suggest an age-related decline in the ability of the liver to synthesize both glycogen and glucose from lactate. The training effect in glyconeogenesis is most likely occurring in the gl uconeogenic pathway as endurance training had little effect on glycoge n synthase activity and trained animals had greater rates of lactate i ncorporation into glucose than untrained at all NE doses.