Effect of indomethacin on hepatic glucose production in vitro: the impact of hepatic glycogen content.
The effect of indomethacin (IND) on glucagon-induced hepatic glucose production (HGP) was studied in the isolated perfused livers of rats. Addition of IND (0.2 mM) to the perfusion medium had no effect on glucagon-stimulated HGP when compared to control experiments without added IND (1.02 +/- 0.17 vs. 1.00 +/- 0.26 mmol per (120 min X 100 g b.w.), respectively; NS). Intravenous pretreatment with both, IND (10 mg/kg b.w.), or vehicle resulted in a reduction in glucagon-induced HGP due to a decrease in hepatic glycogen content. A complete depletion of the hepatic glycogen pool and thus a lack in glucagon-stimulated HGP was observed when IND was given intraperitoneally. These results indicate that the changes in HGP observed after pretreatment with IND may largely if not completely be due to a non-specific depletion in hepatic glycogen content and that IND does not exert a direct influence on HGP.
D000818:Animals; D005934:Glucagon / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects*; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
D008112:Liver Glycogen; D005934:Glucagon; D007213:Indomethacin