Decrease in Glucose Transporter Number in Skeletal Muscle of Mildly Diabetic (Streptozotocin-Treated) Rats*

Abstract

Diabetes is associated with a decrease in glucose uptake into muscle, the primary tissue responsible for whole body glucose uptake in the fed state. To study the basis of such a decrease we estimated the number of glucose transporters in skeletal muscle membranes from control and streptozotocin (STZ)-treated rats. Animals were injected with 65 mg STZ/kg and were clearly diabetic (hyperglycemic and glycosuric) at 1 week. After an overnight fast, animals were killed, and skeletal muscle from hind limbs were removed and used to prepare plasma membranes and internal membranes. The number of glucose transporters was determined by D-glucose-protectable equilibrium binding of [3H]cytochalasin-B. STZ-treated rats showed a 37% decrease in the number of glucose transporters per mg protein in crude membranes. The decrease was more pronounced in plasma membranes (average 50% decrease) than in the intracellular membranes (32% decrease). The reduction in the number of glucose transporters was specific, since it was not paralleled by changes in other plasma membrane markers or in total protein, although plasma membrane protein decreased by 15% in STZ-treated rats. When total recoveries of transporters were calculated (i.e. picomoles of transporters recovered per g tissue), the number of transporters in the plasma membrane fraction from STZ-treated rats was decreased by 68% relative to that in control animals. In the intracellular membranes and in total crude membranes from diabetic rats the transporters were decreased by 45%. This suggests that in STZ-treated rats there is an overall decrease in the number of glucose transporters, and that the plasma membrane is further specifically depleted of transporters. The decrease in glucose transporter number in the plasma membrane could at least in part be the cause of the diminished glucose uptake in diabetic muscle and for overall drop in total body glucose utilization of this condition.