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 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.

NIRS Measurement of O2 Dynamics in Contracting Blood and Buffer Perfused Hindlimb Muscle

“…Preparation of the isolated rat hindlimb and the perfusion apparatus were described in the previous reports [8][9][10]. Fig.…”

Stimulation of Glucose Uptake in Skeletal Muscle Using Bolus or Continuous Insulin Delivery

“…Animals used for perfusion were male Sprague-Dawley rats weighing 130-170 g. All experiments were conducted after an overnight fast. Details of the perfusion technique have been published previously (Lewis et al 1977). Briefly, rats were anesthetized with Pentobarbital (50 mg/kg ip), blood vessels not supplying the hindlimb were ligated, the arterial line introduced into the aorta, the perfusion pump started, and the vena cava cannulated.…”

“…We designed these studies to determine if these two phases of insulin secretion had different effects on glucose transport in skeletal muscle. The isolated perfused rat hindlimb preparation is an excellent model for studying muscle metabolism (Ruderman, Houghton and Hems 1971) and insulin stimulated glucose transport (Lewis, Schultz, Westbie, Gerich and Wallin 1977). In order to mimic the two phases of insulin secretion, insulin was given as boluses or as a continuous infusion, and the glucose uptake by the hindlimb was measured.…”

Role of myoglobin in regulating respiration during muscle contraction

“…Detection of Mb desaturation and oxygenation (Mb-O2 dynamics) is one of the key measurements to understanding the physiological function of Mb and intracellular O2 environment (hypoxic condition) during contraction. Hindlimb perfusion overcomes to detect Mb oxygenation excluding the interference of Hb and is one way out of an extraction of the Mb signal from the NIR composite signal in vivo [32][33][34][35] (Fig. 3).…”