Insulin-stimulated entry of glucose into muscle in vivo as a major factor in the regulation of blood glucose.

1. The entry of glucose into the pectoralis major muscle of living rats was measured over a wide range of plasma glucose concentrations. A technique was used by which steady concentrations of substances are maintained in the circulation throughout the experiments. 2. Raising the concentration of glucose in the plasma caused saturation of the mechanism by which it is transported into muscle. Estimates of the values of the kinetic constants for this transport system were: Kt, 34 mumole ml-1 and V, 1-2 mumole min-1-g-1 muscle. 3. When the plasma glucose concentration was raised up to at least twelve times normal, there was no sign of saturation of the transport system in insulin-treated animals. This finding could be explained if insulin increased greatly both V and Kt for glucose transport. 4. Insulin increased the rate of entry of glucose into muscle over the entire range of plasma glucose concentrations studied (4-8 mumole ml.-1). There was evidence that endogenous insulin produced a similar increase in entry rate some 10 min after the injection of glucose. Fasting, which is associated with a decrease in insulin level, depressed the rate of entry. In hyperglycaemia insulin caused a rise in the concentration of glucose within the muscle cells. 5. The insulin-induced increase in the rate of glucose entry into muscle ensured that approximately 25% of an I.V. dose of glucose entered the muscle cells of insulin-treated animals within one minute. This illustrates the quantitatively important regulatory role that skeletal muscle plays in these circumstances in limiting the extent of a rise in circulating glucose.