Prostaglandin E(2) inhibition of glucagon-induced hepatic gluconeogenesis and cyclic adenosine 3',5'-monophosphate accumulation.
This study examines the role of prostaglandin E(2) (PGE(2)) in modulating hormonal control of hepatic gluconeogenesis. The effects of PGE(2) (2.8 x 10(-6) M), administered alone and in combination with glucagon (1.4 x 10(-9) M), on gluconeogenesis from 20 mM sodium lactate and on cyclic AMP (cAMP) concentration were studied in isolated livers of rats fasted for 24 hr and perfused with Krebs-Ringer bicarbonate (KRB) solution containing 3% albumin and 100 mg/dl of glucose. Samples of perfusate and liver were taken at frequent intervals between 1 and 60 min after KRB (control), PGE(2), glucagon, and PGE(2) + glucagon infusion (ten experiments in each group). Glucagon stimulated more glucose production [45-60 min increment = 80 +/- 7 mg/100 ml (mean +/- standard error)] than did PGE(2) (35 +/- 5 mg/100 ml) or KRB (49 +/- 8 mg/100 ml) (P < 0.01). Concomitant infusion of PGE(2) with glucagon inhibited the glucagon-induced gluconeogenesis (56 +/- 6 mg/100 ml) (P <0.01). Glucagon increased hepatic cAMP concentration approximately 4-fold (control = 354 +/- 29 pmoles/g, maximal stimulation = 1881 +/- 380 pmoles/g). PGE(2) + glucagon reduced cAMP accumulation to approximately 2-fold (control = 365 +/- 31 pmoles/g, maximal stimulation = 806 +/- 99 pmoles/g) (P < 0.05). The data show that PGE(2) inhibits glucagon-mediated gluconeogenesis from lactate. It remains to be determined whether the antigluconeogenic action of PGE(2) is causally related to the inhibition of cAMP content.
Levine
R A
RA
Department of Medicine, State University of New York, Upstate Medical Center, Syracuse, NY 13210, USA.
Schwartzel
E H
EH
D000818:Animals; D000242:Cyclic AMP / Q000032:analysis / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D005215:Fasting; D005934:Glucagon / Q000494:pharmacology*; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000032:analysis / Q000378:metabolism; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D007700:Kinetics; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley
D007773:Lactates; D006003:Glycogen; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose; D015232:Dinoprostone