Insulin-glucose dynamics during flow-through perfusion of the isolated rat hindlimb.

The dose-response relationship between glucose and insulin concentration and utilization in skeletal muscle was examined in hindlimbs of overnight fasted normal male rats. The perfusion was by flow-through technique utilizing an artificial perfusate containing beef erythrocytes. Glucose disappearance correlated significantly with insulin concentration. Insulin effect was detected within 5 minutes. When arterial glucose was 10 mM, glucose disappearance during maximal insulin stimulation was fivefold greater than glucose disappearance in the absence of insulin. A half-maximal effect occurred at an insulin concentration of 411 U per ml. Arteriovenous difference of immunoreactive insulin during a single passage thorugh the hindlimb averaged 16.7% over the range of 50 to 10,000 U per ml. In the presence or absence of insulin, glucose disappearance was positively correlated with glucose concentration up to a glucose concentration range of 30 to 45 mM. In this range and above glucose uptake averaged twelvefold above that observed for 5 mM glucose. When insulin (500 muU/ml) was added at any glucose concentration, glucose disappearance was augmented. The data thus indicate that rat skeletal muscle is a major site of insulin metabolism. In addition to the effect of insulin on glucose uptake by the muscle cell, glucose mass action appears to be quantitatively equipotent.