Effect of DG5128 on epinephrine and glucagon induced glucose output from the isolated perfused rat liver

Abstract The effect of a specific α 2 -adrenergic antagonist 2-[2-(4, 5-dihydro-1.H-imidazol-2-yl)-l-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 × 10 −10 M glucagon. There were no significant changes of the glucose output by 1.4 × 10 −10 M or 7.0 × 10 −11 M glucagon alone. On the other hand, addition of 1mU/ml insulin to the perfusate suppressed the 7.0 × 10 −11 M glucagon-induced glucose output, but failed to decrease the 1.4 × 10 −10 M glucagon effect. DG5128 suppressed further the glucagon (7.0 × 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.