In the Public Domain Effect of Aging on Hepatic Carbohydrate Metabolism in Septic Rats

Aged individuals have diminished resistance to severe sepsis and septic shock. Past work with animals suggested that an important determinant of survival was the ability of the liver to supply glucose. In this study, young adult (3 to 4 months) and old (24 months) Fischer 344 rats were fasted and subjected to cecal incisions producing a rapidly lethal peritonitis. We then determined gluconeogenic intermediates in the liver. In the old rats with peritonitis, hexose-monophosphates (HMP) increased 50 % relative to control liver, whereas in the young animals with peritonitis, the substrate decreased 50%. The accumulation of HMP in the old rat liver cells indicates a failure to dephosphorylate glucose-6-phosphate (G6P). This increase in HMP is associated with a decline in hepatic glucose-6-phosphatase (G6Pase), the final enzyme in the gluconeogenic pathway, and is reflected in a significant reduction in serum glucose in old Fischer 344 rats when compared to young Fischer rats. THE fact that older people are more sensitive to sepsis hasbeen reported by researchers from many medical cen-ters. Findings of two- or threefold increases in mortality in individuals over 50 years of age are not uncommon (Garri-son et al., 1982; McGowan et al., 1975; Schumer, 1976). The reason for this increase has been postulated to be depressed immunology, inadequate stress hormone re-sponses, or loss of enzyme or metabolic reserves (Linn & Jensen, 1983; Sapolsky et al., 1983). We have been inter-ested in the effect of sepsis on gluconeogenesis and glycoly-sis and previously noted that in older postmature rats (12 months) hepatic metabolic reactions to E. coli endotoxin were more severe than in young adult animals (2 to 4 months) (Kuttner et al., 1985). Laboratory investigations of different animal shock models (Yates et al., 1980) agree with observations of human patients that hypoglycemia frequently accompanies the late preterminal stage of endotoxemia and sepsis due to gram-negative bacteria (Berkman et al., 1985; Holloway &amp