Effects of insulin on glucose metabolism by the perfused normal rat liver

Abstract

Isolated livers taken from fed and fasted normal rats were perfused for 4 hr. in a medium consisting of diluted rat blood and glucose at "low" ([image]110 mg/100 ml) and "high" ([image]450 mg/100 ml) glucose concentrations, using glucose-1-14C, glucose-6-14C and acetate-3H as metabolic tracers. The most consistent effects of insulin, seen in experiments with fasted liver donors at low starting glucose concentration, were a lowering of the blood glucose at 2 and 4 hr., and stimulation of fatty acid synthesis from both glucose and acetate. The 14C data suggested mainly an inhibition of glucose release, although there were no concomitant insulin effects on glycogen content or on urea production. Raising the perfusate glucose concentration increased the incorporation of glucose into glycogen and CO2, and of both glucose and acetate into fatty acids. It also increased the formation of acetyl coenzyme A from pyruvate, as evidenced from the ratio of 14C to 3H in isolated fatty acids. Insulin did not modify this ratio. A unitary hypothesis of insulin action cannot be deduced from these results.