Insulin-Glucose Dynamics during Flow-Through Perfusion of the Isolated Rat Hindlimb[*]

Abstract

The dose-response relationship between glucose and insulin concentration and utilization in skeletal muscle was examined in hind limbs 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 µU per ml. Arteriovenous difference of immunoreactive insulin during a single passage through the hindlimb averaged 16.7% over the range of 50 to 10,000 µU 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 µU/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.

Key words

Flow-Through Perfusion - Rat Hindlimb Preparation - Beef Erythrocytes - Glucose and Insulin Disappearance - Fasting - Synthetic Medium

1 This study was supported through funds provided by the Bureau auf Medicine and Surgery, Navy Department, for CIP-5-48-387. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Navy Department or the naval service at large.

1 This study was supported through funds provided by the Bureau auf Medicine and Surgery, Navy Department, for CIP-5-48-387. The opinions or assertions contained herein are the private ones of the authors and are not to be construed as official or as reflecting the views of the Navy Department or the naval service at large.

2 Present address: LCDR D.K. Westbie, MC, USN, Department of Metabolism and Endocrinology, Naval Regional Medical Center, San Diego, California 92134 (USA)