Hypoglycemic Effect of Ouabain in Dogs

Abstract

I t has been reported that ouabain exerts in vitro metabolic effects characterized by an inhibition of spontaneous (1) and epinephrinestimulated glycogenolysis (2,3) and lipolysis (2,4,5). All these in vitro studies were performed with high concentrations of ouabain M ) . The purpose of the present study was to determine if ouabain exerted metabolic effects in intact animals in a dosage much lower than that used in vitro, and if a similar interaction with the metabolic effeot of epinephrine occurred. Assuming that the total dose of ouabain administered to the animals (1 &g/kg per min for 60 min) accumulated in a volume of water approximating extracellular water, the final concentration would be about lo-' M . This dose is at least 100 times less than that used in vitro.Methods. Experiments were performed on 14 pedigreed male beagles less than 1 year old and fasted for 18 hours before the experiment. The animals were anesthetized with 35 mg/kg of Na pentobarbital, intravenously administered, and intubatd with a cuffed endotracheal tube. Mechanical ventila&ion with 100% 02 was administered at constant rate and volume so as to maintain normal acid-base equilibrium and 0 2 saturation in arterial blood throughout the experiment. Muscle relaxation was maintained with succinylcholine chloride. Each animal served as his own control and was studied twice at no less than a week's interval according to a protocol previously described ( 6 ) .Two series of experiments were performed. I n the first series of experiments on 6 dogs, following the control period, ouabain (1.0 pg in 0.1 ml of saline/kg per min) was administered i.v. for 60 min. Observations were M to *This work was supported, in par,t, by Army Contract DADA-17-67-C-7126 and N.I.H. G,rant GM-09069-05.continued for 60 min following the end of ouabain administration. I n the control experiment, the same volume of saline as of ouabain was administered. In the second series of experiments on 8 dogs, the effect of ouabain on the metabolic activity of epinephrine was studied. After the control period, ouabain (1.0 Fg,kg per min) was administered to the mi-ma1 for 60 min in the same volume as given in the first series. During the last 30 min of this infusion, epinephrine (0.8 pg in 0.1 ml of saline/kg per min) was administered intravenously. Observations were continued for 60 min following the end of drug infusion. In the control experiment performed on the same animal, a volume of isotonic saline equal to that of ouabain was given while the same dose of epinephrine was administered. As in the first series, the sequence of ouabain-saline administration was reversed from one animal to the next. Specific methods of measurements have been described in previous publications (6). The data was analyzed statistically according to the Student t test. The significance of differences between paired measurements was calculated by the method of difference between correlated pairs. The p was evaluated within 5% limit of confidence.Results. Ouabain administration. Mean blood pressure i...

Effect of Ouabain on Insulin Secretion in Man

“…Triner, Kypson & Nahas (1968) reported that the intravenous infusion of ouabain in a dose of 1 pglmin-' kg-' for 1 h resulted in a significant decrease (30%; P<0*05) of blood glucose concentration in anaesthetized dogs. Loubatieres et al (1968) and Triner et al (1969) subsequently demonstrated that the fall in blood glucose concentration observed during similar ouabain infusions was associated with a significant increase in plasma insulin concentration in the portal vein.…”

Effects of Ouabain on Insulin Secretion in the Dog

“…In the first series of experiments, the hypoglycemic effect of ouabain in ten dogs was compared to that of ouabain combined with insulin or propranolol following a protocol previously described (12). Each animal served as his own control and was studied twice at a week's interval.…”

“…This dose, which corresponds approximately to four times the therapeutic dosage, did not produce any marked electrocardiographic or plasma potassium changes, but caused a significant decrease in glucose and glycerol plasma concentrations. The same dose of ouabain significantly inhibited the lipolytic and glycogenolytic effects of epinephrine (12). The purpose of the present series of experiments was to investigate the mechanism of the hypoglycemic effect of ouabain, i.e., to establish whether it is a direct effect of the drug on glucose metabolism or whether it is mediated through insulin.…”

“…To study the metabolic effects of ouabain in vivo, experiments were performed in dogs which were given ouabain, 1.0 /i,g/kg/min iv for 60 minutes (12), a substantially lower dose than that used in vitro. This dose, which corresponds approximately to four times the therapeutic dosage, did not produce any marked electrocardiographic or plasma potassium changes, but caused a significant decrease in glucose and glycerol plasma concentrations.…”