HORMONAL-REGULATION OF HEPATIC GLUCONEOGENESIS - INFLUENCE OF AGE ANDTRAINING

The contributions of three major gluconeogenic regulators, glucagon (1 0(-7) M), alpha-adrenergic agonist phenylephrine (10(-5) M), and P-ago nist isoproterenol (10(-5) M) to hepatic glucose synthesis in liver sl ices from Fischer 344 rats were examined in relation to age and endura nce training. Young (4 mo), middle-aged (12 mo), and old (22 mo) male Fischer 344 rats (n = 66) were divided into trained or sedentary group s. Trained animals were run 10 wk on a treadmill at 75% of maximal cap acity, 1 h/day, 5 days/wk. Animals were killed at rest, and sections o f liver were removed and sliced in a tissue microtome. Slices were inc ubated in L-[U-C-14]lactic acid, Ringer solution, and one of the afore mentioned gluconeogenic regulators. Rates of lactate incorporation int o glucose and glycogen were significantly greater in young compared wi th old animals for all three regulators in both trained and untrained animals. Training elicited a 35, 52, and 63% improvement in lactate in corporation into glucose compared with untrained when the livers of yo ung (16.9 +/- 1.2 vs. 10.9 +/- 1.1 mu mol . g protein(-1). min(-1)), m iddle-aged (12.8 +/- 1.3 vs. 6.1 +/- 1.2 mu mol . g . protein(-1). min (-1)), and old (11.2 +/- 1.1 vs. 4.1 +/- 0.6 mu mol . g . protein(-1). min(-1)) animals, respectively, were incubated in glucagon. Rates wit h phenylephrine followed a similar pattern to that with glucagon acros s age and training, but absolute rates were significantly lower. No tr aining effect in gluconeogenic rate was found when liver was incubated in the presence of isoproterenol. It is concluded that the gluconeoge nic capacity of liver declines with age regardless of the gluconeogeni c regulator and that training was able to partially offset age-related declines in glucagon-stimulated and alpha-receptor-mediated gluconeog enesis.