Time course of changes in gluconeogenesis from various precursors in chronically endotoxemic rats.

Rates of gluconeogenesis (GNG) from lactate and triosephosphate precursors were measured in hepatocytes isolated from rats that have received endotoxin or physiological saline by continuous infusion from an implanted pump. Six hours after the onset of infusion (day 2 postsurgery) GNG from lactate was significantly elevated in hepatocytes of endotoxemic (ET) animals. By 24 hours later, the gluconeogenic rate was depressed, compared to cells of NaCl-infused controls. However, providing ET cells with lactate at concentrations found in the in vivo milieu resulted in glucose production at rates not different from those of control cells incubated at their respective in vivo (lower) substrate levels. On day 2 postsurgery, ET rats were hyperglycemic and hyperlactacidemic; on day 3 the elevated blood lactate concentration was maintained, but the plasma glucose values were not different from those of NaCl controls. The glucagon-induced increment in glucose synthesis was depressed in cells of ET rats both on day 2 and day 3 postsurgery, although the total amount of glucose released was significantly less only on day 3. The pattern of norepinephrine stimulation was similar to that of glucagon, except for the increase above the basal rate of GNG on day 3 being the same for control and ET cells. GNG was also assessed from oxidized substrates (fructose (F) and dihydroxyacetone (DHA] and reduced substrates (sorbitol and glycerol) entering the pathway at the triosephosphate level. On day 2 both cell populations produced glucose from each of the four precursors at comparable basal rates.(ABSTRACT TRUNCATED AT 250 WORDS)