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

Abstract

Sumida, Ken D., Steven M. Arimoto, Michael J. Catanzaro, and Frank Frisch. Effect of age and endurance training on the capacity for epinephrine-stimulated gluconeogenesis in rat hepatocytes. J Appl Physiol 95: 712-719, 2003; 10.1152/japplphysiol.01125.2002.-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-14 C]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 Ϯ 6.2 nmol/mg protein) compared with young controls (C) (78.2 Ϯ 6.0 nmol/mg protein). The basal HGP was also significantly greater for old T (97.3 Ϯ 5.9 nmol/mg protein) compared with old C (72.2 Ϯ 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 Ϯ 6.5 nmol/mg protein) compared with young C (110.9 Ϯ 4.8 nmol/mg protein). Similarly, the V max was significantly greater for old T (138.2 Ϯ 5.0 nmol/mg protein) compared with old C (103.9 Ϯ 2.5 nmol/mg protein). Finally, there was an increase in the EC 50 from the hepatocytes of old T (56.2 Ϯ 6.2 nM) compared with young T (32.6 Ϯ 4.9 nM). In like manner, there was an increase in the EC 50 from the hepatocytes of old C (59.7 Ϯ 5.8 nM) compared with young C (33.1 Ϯ 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 EC 50 that is independent of training status. liver; lactate; glucose production; exercise THE BRAIN AND NERVE TISSUES depend on the maintenance of blood glucose to sustain a concentration gradient for extraction (16). When liver glycogen stores become depleted, hepatic gluconeogenesis becomes an essential component in an organism's ability to maintain blood glucose levels. Endurance training has been shown to resist the decrements in blood glucose concentrations during prolonged exercise despite depletion of hepatic glycogen stores (7). Our laboratory has previously demonstrated an enhanced hepatic gluconeogenic capacity attributable to endurance training in rats (7,32,33). The augmentation in glucose production ability in the liver could help to account for the maintenance of blood glucose levels in trained animals during prolonged exercise when hepatic glycogen stores become depleted (8). Conversely, recent reports have demonstrated age-related declines in hepatic gluconeogenic capacity (25)(26)(27). This loss in liver function could compromise the ability of an elderly individual to respond to a given stress. However, reports from demonstrate that endurance training can help to offset the age-related decline in the liver's glucose production capacity.Hor...

Alterations of epinephrine-induced gluconeogenesis in aging

“…To understand the reasons for the reduced response to β 2 -AR-stimulated intracellular function, aged rat hepatocyte viability, receptor density, receptor binding affinity, and adenylate cyclase activities were studied (Morgan et al, 1983;Fraeyman et al, 2000). The β 2 -AR number, the density, the Gs activity, and the protein levels were all unchanged in aging (Dax et al, 1987;Eakes et al, 1996;Marker et al, 1998;Sumida et al, 2003).…”

“…age related decrease in the β 2 adrenergic receptor (AR), adenylate cyclase, or to Gαs expression (Dax et al, 1981Fraeyman et al, 2000. In contrast, it has been suggested that expressions of the β 2-AR, adenylate cyclase or Gαs either increase or do not change with aging (Dax, 1987;Eakes, 1996;Marker, 1998;Sumida, 2003;Jang, 2006). Thus, the questions of why and how epinephrine becomes less potent in the gluconeogenesis response in aging remain unanswered.…”

Epinephrine responsiveness is reduced in livers from trained mice

“…In trained subjects, the lipolytic response of adipocytes to epinephrine was increased in comparison to fat cells from sedentary subjects (Riviere et al, ). Similarly, epinephrine stimulated gluconeogenesis was greater in hepatocytes isolated from trained compared to sedentary rats (Sumida et al, ), though it should be noted that this has not been a universal finding (Podolin et al, ).…”

“…Exercise training influences the metabolic responsiveness to catecholamines in adipose tissue, skeletal muscle, and the liver (Plourde, Rousseau-Migneron, & Nadeau, 1993;Podolin, Gleeson, & Mazzeo, 1996;Riviere, Crampes, Beauville, & Garrigues, 1989;Sumida, Arimoto, Catanzaro, & Frisch, 2003). For example, isoproterenol-stimulated adenylyl cyclase activity was significantly elevated in soleus muscles from trained compared to sedentary rats (Plourde et al, 1993).…”

Single‐injection glucose kinetics with compartmental modelling during rest and low‐intensity exercise in horses

“…This augmentation may be attributable to redistribution of vascular volume increasing glucose availability to muscle tissue. Catecholamines may also increase EGP directly or by suppressing insulin while increasing glucagon (Wasserman et al 1989;Gustavson et al 2003;Sumida et al 2003).…”