In vitro autoregulation of glucose utilization in rat soleus muscle

The possibility that glucose may directly regulate its rate of utilization in skeletal muscle was investigated in vitro with the rat soleus muscle. Preincubation of the muscles with varying glucose concentrations modulated the rate of glucose utilization through the glycolytic pathway during a subsequent incubation. At glucose concentrations below approximately 3.0 mM, utilization was maximal (26.8 +/- 2.4 and 87.5 +/- 4.8 nmol X g-1 X min-1 when assayed in the presence of 0.5 and 5.0 mM glucose, respectively). Preincubation with higher glucose concentrations (up to 20 mM) reduced the utilization by 40-60% in a biphasic manner: a rapid fall between 1 and 4 mM, followed by a gradual approximately 2% decrease per each millimolar increase of glucose. The effect of preexposure to glucose was not due to substrate dilution by the remaining glucose in the extracellular or intracellular space of the muscle. The uptake of the nonmetabolizable glucose analogues 3-O-methylglucose and 2-deoxyglucose was also modulated by extracellular glucose in a similar manner. Thus, the regulatory site seems to reside in the transport function of the hexose. The ATP content was very similar in muscles preexposed to 1.0 and 15.0 mM glucose for 3 h and therefore does not seem to be the mediator of the glucose effect. This substrate regulation of the rate of glucose transport and of the glycolytic flux may be operative in the in vivo glucose homeostatic system and may contribute to the reduced peripheral glucose utilization observed in diabetes.