ROLE OF PROSTAGLANDINS IN MEDIATING ALTERATIONS IN GLUCOSE-METABOLISMDURING ACUTE ENDOTOXEMIA IN THE RAT

We determined the role of prostanoids in mediating alterations in gluc ose metabolism during lipopolysaccharide (LPS)-induced (1 mg/ kg, LD(1 0)) acute endotoxemia in chronically catheterized awake rats. Basal gl ucose turnover (R(t), infusion of[5-H-3]glucose), in vivo insulin acti on on overall glucose utilization under normoglycemic conditions (eugl ycemic clamp), whole body glycolysis, and muscle glycogen synthesis we re determined in four groups of rats. These groups received 1) LPS (LP S rats, n = 6); 2) saline (control rats, n = 6); 3) indomethacin and L PS (INDO and LPS rats, n = 6); or 4) saline and indomethacin (INDO con trol rats, n = 6). In the fasted rats, LPS induced hyperthermia, hypot ension, and hyperglycemia. These changes were associated with glycogen depletion in both skeletal muscle and liver and with increased R(t). During hyperinsulinemia, whole body glucose disposal was decreased by 37% due to decreased muscle glycogen synthesis and glycogen synthase a ctivity whereas the rate of whole body glycolysis was normal. INDO abo lished hyperthermia, hypotension, and hyperglycemia but did not improv e whole body insulin sensitivity, muscle glycogen synthesis, or glycog en synthase activity. These data indicate that prostanoids mediate hyp otension, transient fasting hyperglycemia, and fever during LPS-induce d acute endotoxemia. They do not, however, explain insulin resistance under these conditions.