Effects of pancreatectomy, tolbutamide and insulin on glucose fluxes in chickens

The effects of pancreatectomy and of injection of insulin or tolbutamide on glucose fluxes in chickens were examined. This was prompted by earlier observations that tolbutamide seems not to require the presence of pancreatic insulin for its acute hypoglycaemic action in this species. Rates of appearance (Ra) and disappearance (Rd) of glucose were estimated by isotope dilution using [14C]glucose in single-injection experiments and [14C]glucose and [6−3H]glucose in priming-injection + constant-infusion experiments. Six hours after sub-total pancreatectomy (splenic lobe remained in situ), chickens were hyperglycaemic (16·7 v. 10·4 mmol glucose/l in controls), had a larger sampled glucose pool (4·41 v. 3·10 mmol) and a higher average rate of glucose utilization (41·7 v. 33·3 μmol/kg per min) than sham-operated controls as estimated in single-injection experiments. Tolbutamide (50 mg/kg injected i.v.) reduced Ra in intact chickens from 33·9 to 1·1 μmol/kg per min and reduced Ra in pancreatectomized chickens from 42·2 to 10·2 μmol/kg per min. In priming-injection + constant-infusion experiments tolbutamide again reduced Ra significantly. In all cases Rd tended to fall, apparently as a result of the developing hypoglycaemia. Tolbutamide did not affect the volume of extracellular fluid (sucrose space). In single-injection experiments, insulin (1 unit/kg injected i.v.) reduced Ra by 56% and transiently increased Rd by 39%. It was concluded that pancreatectomy and injection of insulin or tolbutamide produce responses in glucose movements in chickens that are qualitatively similar to those in mammals. In chickens the hypoglycaemic action of tolbutamide, which persists in the absence of the pancreas, depends on an inhibition of glucose release by the liver.