Role of prostaglandins in mediating alterations in glucose metabolism during acute endotoxemia in the rat.
We determined the role of prostanoids in mediating alterations in glucose metabolism during lipopolysaccharide (LPS)-induced (1 mg/kg; LD10) acute endotoxemia in chronically catheterized awake rats. Basal glucose turnover (Rt, infusion of [5-3H]glucose), in vivo insulin action on overall glucose utilization under normoglycemic conditions (euglycemic clamp), whole body glycolysis, and muscle glycogen synthesis were determined in four groups of rats. These groups received 1) LPS (LPS rats, n = 6); 2) saline (control rats, n = 6); 3) indomethacin and LPS (INDO and LPS rats, n = 6); or 4) saline and indomethacin (INDO control rats, n = 6). In the fasted rats, LPS induced hyperthermia, hypotension, and hyperglycemia. These changes were associated with glycogen depletion in both skeletal muscle and liver and with increased Rt. During hyperinsulinemia, whole body glucose disposal was decreased by 37% due to decreased muscle glycogen synthesis and glycogen synthase activity whereas the rate of whole body glycolysis was normal. INDO abolished hyperthermia, hypotension, and hyperglycemia but did not improve whole body insulin sensitivity, muscle glycogen synthesis, or glycogen synthase activity. These data indicate that prostanoids mediate hypotension, transient fasting hyperglycemia, and fever during LPS-induced acute endotoxemia. They do not, however, explain insulin resistance under these conditions.
Virkamäki
A
A
Second Department of Medicine, University of Helsinki, Finland.
Yki-Järvinen
H
H
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D004731:Endotoxins / Q000097:blood*; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism; D006339:Heart Rate; D007213:Indomethacin / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000378:metabolism; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D004731:Endotoxins; D008070:Lipopolysaccharides; D011453:Prostaglandins; D006003:Glycogen; D005947:Glucose; D007213:Indomethacin