Insulin control of hepatic glucose production

Insluin injected intravenously caused a rapid, marked decrease in hepatic glucose secretion in the rabbit, as determined by an isotope-dilution procedure. This was associated with a decrease in the concentrations of gluconeogenic intermediates from phosphoenolpyruvate to triose phosphates, inclusive, compatible with inhibition of gluconeogenesis at phosphoenolpyruvate carboxykinase. The concentration of glucose 6-phosphate was unaltered but that of hepatic glucose was reduced. The specific activities of the hexose phosphates, relative to that of liver glucose, were the same in control and insulin-treated animals. These observations can be explained by a decrease in the activity of glucose-6-phosphatase. It is concluded that this enzyme is a control point for hepatic glucose production and is inhibited by insulin. In the rat, insulin produced a rapid fall in blood sugar. The hepatic glucose output remained normal despite a fall in hepatic glucose 6-phosphate concentration during the initial period of insulin action. This suggests that glucose-6-phosphate returned to normal with no change in the rate of glucose production. The data suggest that in the rat, insulin produces a transient increase in glucose-6-phosphatase activity.