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.
Department of Medicine, State University of New York, Upstate Medical Center, Syracuse, NY 13210, USA.
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Levine
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Schwartzel
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