AGING, ACUTE OXIDATIVE INJURY AND HEPATOCELLULAR GLUCOSE-TRANSPORT INTHE RAT

We studied the effects of aging and acute exposure to hydrogen peroxid e on hepatocellular glucose transport to determine whether (1) acute o xidative stress impairs glucose transport, (2) aging is associated wit h reduced glucose transport and (3) there are similarities between the se changes that may provide insight into the aging process. Glucose tr ansport was measured in the perfused livers of young and aged rats usi ng the multiple indicator-dilution method. There were significant redu ctions in the rate constants for glucose influx (P < 0.001) and a sign ificant increase in the extracellular volume in the livers from aged r ats (aged: 0.39 +/- 0.05 ml/g, young: 0.27 +/- 0.04 ml/g), However, th e K-m and V-max for glucose influx in the livers from aged rats (44 +/ - 22 mM, 7.1 +/- 1.4 mu mol.s(-1)g(-1) respectively) were not signific antly different from the values in young rats (64 +/- 20 mM, 8.8 +/- 1 .3 mu mol.s(-1)g(-1)). In the livers of young rats, treatment with hyd rogen peroxide caused a significant reduction in glucose transport fro m 1.18 +/- 0.22 to 0.49 +/- 0.25 mu mol.s(-1)g(-1). This was partly re stored to 0.69 +/- 0.20 mu mol.s(-1)g(-1) by occluding the outflow cat heter and expanding the extracellular space. Thus, although aging did not influence the rate of glucose transport in the perfused rat liver, this may be due to a compensatory age-related increase in the extrace llular volume. In conclusion, the changes observed in hepatocellular g lucose transport in the aged liver could be simulated by oxidative inj ury in the young liver, suggesting a role for oxidative injury in the aging process.