Enhanced Sugar Uptake Fails to Simulate the Insulin Effect on Lipogenesis in the Isolated Perfused Rat Liver

Abstract

Large quantities of glucose and fructose were infused without insulin into isolated livers of fasted normal and fed diabetic rats as a test of the widely accepted theory that the single primary role of insulin is to speed the entry of glucose into the cell. The liver disposed of large quantities of hexose in most cases without simultaneously increasing, as with insulin, the rate of incorporation of acetate-1-C¹⁴ into fatty acids. Much of the sugar was transformed to glycogen and CO₂ without entering the pathways of fatty acid or ketone body synthesis, or influencing the conversion of acetate to these products. With livers of fasted normal rats, massive fructose infusion significantly inhibited urea formation and reduced the incorporation of acetate into glucose and plasma protein. The dissociation between carbohydrate balance and lipogenesis suggests that insulin has some primary action other than making more sugar available in metabolism. It is suggested that there is an anatomic separation of metabolic pathways in the liver, and that insulin serves to facilitate glucose transport between them.