The comparative effects of barbituric acid and phenobarbital on blood glucose and insulin secretion in mice

Abstract

The effects of barbituric acid and phenobarbital upon carbohydrate metabolism in mice were compared. An intraperitoneal dose of 100 mg/kg of barbituric acid increased blood glucose concentrations during an intravenous glucose tolerance test, but did not alter the rate of glucose disappearance from the blood. Barbituric acid also antagonized the hypoglycemic effect of intravenously administered tolbutamide. The same dose of phenobarbital had no effect. An in vitro concentration of 100 mug/ml of barbituric acid decreased the responsiveness of isolated mouse pancreatic islets to glucose stimulation (3.0 mg/ml D-glucose). Again phenobarbital, 100 mug/ml, was without effect. The structural similarities between barbituric acid, tolbutamide and alloxan suggest that the effects observed in these experiments might reflect a competition for binding to reactive sites on or within the pancreatic B-cell.

Barbiturates inhibit ATP‐K+ channels and voltage‐activated currents in CRI‐G1 insulin‐secreting cells

“…This agrees with the findings of Dean & Matthews (1972), who have shown that this compound induces a rapid depolarization of the fl-cell and suggested that it is mediated through an interaction with a specific membrane component. In addition, Mennear et al (1976) proposed that barbituric acid, tolbutamide and alloxan compete for the same site on the f-cell membrane. In view of the findings presented here, this may be the ATP-K+ channel.…”

“…For example, pentobarbitone has been reported to decrease insulin levels in vivo after glucose load, in dogs (R.enauld & Sverdlik, 1975), and in rats (Aynsley-Green et al, 1973) and to reduce insulin release from mouse pancreatic fl-cells in vitro (Panten et al, 1973;Hellman, 1977). However, Aynsley-Green et al (1973) have observed that intravenous pentobarbitone does not affect blood glucose in starved rats, and Mennear et al (1976) found that pentobarbitone has no effect on blood glucose concentration during intravenous glucose tolerance tests in mice.…”