title: Effect of DG5128 on epinephrine and glucagon induced glucose output from the isolated perfused rat liver.
abstract: The effect of a specific alpha 2-adrenergic antagonist 2-[2-(4,5-dihydro-1.H-imidazol-2-yl)-1-phenyl-ethyl] pyridine dihydrochloride sesquihydrate (DG5128), on the glucose output by epinephrine and/or glucagon was studied using the perfused rat liver. The administration of DG5128 alone did not affect the glucose output. However, DG5128 produced a significant inhibition of the increased glucose output when induced by 10(-6) M epinephrine alone or 10(-6) M epinephrine plus 1.4 x 10(-10) M glucagon. There were no significant changes of the glucose output by 1.4 x 10(-10) M or 7.0 x 10(-11) M glucagon alone. On the other hand, addition of 1 mU/ml insulin to the perfusate suppressed the 7.0 x 10(-11) M glucagon-induced glucose output, but failed to decrease the 1.4 x 10(-10) M glucagon effect. DG5128 suppressed further the glucagon (7.0 x 10(-11) M)-induced increase of glucose output in the presence of insulin. These results suggest that DG5128 produces a hypoglycemic effect partly through an inhibition of the increased hepatic glucose output elicited by epinephrine and glucagon.
authors.affiliation: Division of Metabolism and Clinical Nutrition, Kyoto University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Usami
authors.forename: Y
authors.initials: Y
authors.lastname: Seino
authors.forename: T
authors.initials: T
authors.lastname: Taminato
authors.forename: M
authors.initials: M
authors.lastname: Seno
authors.forename: G
authors.initials: G
authors.lastname: Koh
authors.forename: M
authors.initials: M
authors.lastname: Ohno
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Imura
mesh_terms: D000818:Animals; D004837:Epinephrine / Q000494:pharmacology*; D005934:Glucagon / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D007004:Hypoglycemic Agents; D007093:Imidazoles; C032368:midaglizole; D005934:Glucagon; D005947:Glucose; D004837:Epinephrine