Metabolic Effects of γ-Guanidinobutyramide. I. In Vivo Study in Anesthetized Dogs

Abstract

γ-Guanidinobutyramide (HL 523) was infused intravenously for 2 hr in anesthetized dogs. It provoked progressive hypoglycemia which was associated with an increased rate of glucose utilization and increased hepatic glucose output. The infusion of HL 523 also caused increases in the plasmatic level of insulin and free fatty acids, blood pressure and hematocrit. The increased rate of glucose utilization appeared to be due not only to the insulinotropic action of HL 523 but also to a direct effect of the drug upon glucose uptake by peripheral tissues. Thus, the hypoglycemic action of HL 523 persisted despite prior administration of propanolol which resulted in reduced levels of circulating insulin. No satisfactory explanation could be found for the adrenergic-like effects, such as increase in the level of free fatty acids, blood pressure and hematocrit. 1 This work was supported in part by a grant from the Fonds National de la Recherche Scientifique (W.J.M.), and by the association contract Euratom-Universities of Pisa and Brussels (026-63-04 BIAC).