Glucocorticoid action on rat hepatic glycolytic intermediates during experimental peritonitis.

Previous work demonstrated that glucose-6-phosphate (G6P) and fructose-6-phosphate (F6P) levels declined early in endotoxemic and septic livers. Since glucocorticoids are known to support hepatic gluconeogenesis in endotoxemia, these agents were tested in a peritonitis model produced by cecal incision in fasted adult male rats. Dexamethasone sodium phosphate (DMS) and methylprednisolone sodium succinate (MPS) were given in doses of 1 mg and 3 mg, respectively, per 100 gm rat weight at time of incision. Freeze-clamp biopsy samples obtained at 5 hr were enzymatically assayed. G6P and F6P in sepsis (N = 12) decreased 50% and 36%, respectively, below sham-operated control values (N = 15) of 236 and 61 nmole/gm wet tissue. The decrease with DMS was 20% and 16% and with MPS was 22% and 23%, showing partial restoration to normal levels. Phosphoenolpyruvate (PEP) did not decline in the moderate, non-terminal stage of peritonitis when compared to the control value (N = 19) of 209 nmole/gm. Treatment with glucocorticoids raised PEP to supernormal levels: DMS (N = 19) a 63% elevation, MPS (N = 12) a 51% elevation above controls in peritonitis rats. The glucocorticoid effect was similar in both rapid endotoxic and the slow peritonitis shock models. It is concluded that hexose monophosphate (HMP) increase is secondary to the support of PEP synthesis with glucocorticoid treatment. Changes in sham-operated control rat livers treated with glucocorticoids did not reach statistical significance.