THE PERIPHERAL ACTION OF TOLBUTAMiDE IN DOMESTIC FOWL1

Abstract

The effect of tolbutamide was studied in chickens which had been functionally hepatectomized or both depancreatized and hepatectomized. The effects of simultaneous injection of Orinase (tolbutamide) and insulin on blood glucose, non-protein nitrogen (NPN), and inorganic phosphate in the intact fowl were also investigated. Hepatectomized fowl responded to 10 mg Orinase /kg body weight; the degree and pattern of response was almost identical with that of intact fowl of the same age. Hepatectomized birds proved to be hypersensitive to insulin, since an insulin dose that produced the same degree of hypo-glycemia as Orinase in intact birds had a much more profound and prolonged hypoglycemic effect in hepatectomized birds. Birds which were depancreatized and later functionally hepatectomized also responded with hypoglycemia to Tolbutamide injection. Unless there is an extra-pancreatic and extrahepatic source of insulin in the chicken, it is unlikely that the action of Orinase involves stimulation of insulin formation and/or secretion. Intensification of insulin activity by Orinase was demonstrated in intact birds which were injected with the two drugs simultaneously. Both blood glucose and NPN were depressed to a greater degree than when either insulin or Orinase was injected alone. In contrast to insulin, Orinase appears to be ineffective in decreasing blood inorganic phosphorus in the fowl. The action of Orinase, therefore, appears to be mediated through the peripheral tissues.