Effects of Ouabain on Insulin Secretion in the Dog

¹ Departments of Anesthesiology, Medicine, and Surgery, College of Physicians and Surgeons, Columbia University New York, N. Y. 10032

The mechanism of the previously reported hypoglycemic effect of ouabain was studied in dogs. Ouabain (1.0 µg/kg/min infused intravenously for 60 minutes) combined with insulin or propranolol caused a greater and more prolonged decrease in blood glucose than either of the drugs administered separately. In intact dogs, ouabain changed significantly portohepatic venous differences in plasma glucose from +6.6 to -13.6 mg/100 ml and in K⁺ from -0.03 to -0.4 mEq/liter. In pancreatectomized animals, ouabain did not cause any significant decrease in peripheral glucose level, and the portohepatic differences in plasma glucose changed from +5.3 to +30.2 mg/100 ml and the differences in K⁺ from -0.01 to +0.2 mEq/liter. These changes, indicating an increased release of glucose and K⁺ by the liver in the pancreatectomized dog, were also observed in isolated rat liver perfused with ouabain 10^-6M. Glucose uptake of the hindlimb increased significantly during the infusion of ouabain in normal dogs, but did not change in pancreatectomized dogs. Ouabain caused a significant increase in plasma insulin in portal blood (+155%). These results demonstrate that the observed metabolic effects of ouabain in the dog are mainly mediated by insulin and that ouabain increases the secretion of insulin in intact dogs.

Submitted on May 1, 1969
Accepted on June 12, 1969