Indomethacin and salicylate decrease epinephrine-induced glycogenolysis.
Epinephrine (E) produces an immediate (0-30 minutes) rise in hepatic glucose production (Ra), largely due to activation of glycogenolysis; thereafter, E-stimulated gluconeogenesis becomes the major factor maintaining glucose production. To investigate the possible role of arachidonic acid metabolites on Ra during E stimulation, we infused E in trained conscious dogs before and during administration of two inhibitors of arachidonic acid metabolism, indomethacin (INDO) and salicylate (S). On separate days, experimental animals were treated with both oral and IV INDO and oral acetylsalicylic acid and IV sodium salicylate. Ra and glucose utilization (Rd), both in mg x kg-1 min-1, were calculated by isotope dilution using 3-3H-glucose. After achieving steady state specific activity, control (C) and experimental animals (n = 6 per group) received E (0.1 ug x kg-1 min-1) for 150 minutes, raising plasma levels to approximately 1500 pg/mL in each group. In C, plasma glucose (G; mg/dL) rose by 17 +/- 5 at 10 minutes and 19 +/- 3 at 20 minutes due to an initial spike in Ra (2.7 +/- 0.2 to 4.9 +/- 0.5; P less than 0.01) at 10 minutes. INDO and S treatment attenuated this initial (10-20 minutes) rise in G (P less than 0.05) due to a lower stimulated Ra at 10 minutes (3.3 +/- 0.1 with INDO; 3.0 +/- 0.5 with S; P less than 0.05). After 20 minutes Ra was not different in the 3 groups; no overall differences in Rd, glucose clearance, or plasma insulin levels occurred with INDO or S treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003864:Depression, Chemical; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology*; D007263:Infusions, Parenteral; D007328:Insulin / Q000097:blood; D008112:Liver Glycogen / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011865:Radioisotope Dilution Technique; D012459:Salicylates / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D008112:Liver Glycogen; D012459:Salicylates; D005947:Glucose; D007213:Indomethacin; D004837:Epinephrine