In Vitro Effects of Sulfonylurea on Glucose Transport and Translocation of Glucose Transporters in Adipocytes From Streptozocin-Induced Diabetic Rats

Abstract

The in vitro effects of the sulfonylurea glyburide on insulin binding and action were comparedin adipocytes from control and nonketotic streptozocininduced diabetic rats. Adipose tissue from control and diabetic animals was maintained in the absence or presence of 2 μg/ml glyburidefor 20 h. Insulin binding and insulin-stimulated glucose transport were examined in adipocytes prepared from this tissue. As expected, insulin binding was increased in adipocytes from diabetic animals. Exposure of tissue to glyburide did not influence insulin binding in either control or diabetic cells. Glucose transport activity of diabetic cells, assessed with 2-deoxyglucose, was decreased 30–40% in both the absence (basal) and presence of insulin compared with controls. Glyburide potentiated insulin's effects in both control (15–20%) and diabetic (30–40%) adipocytes. As a result, glucose transport activity in glyburide-treated diabetic cells was restored to a level similar to that of control cells not exposed to the drug. The mechanism by which glyburide potentiatedglucose transport activity was examined with the D-glucose-displaceable cytochalasin B-binding technique to measure glucose-transporter concentration in membranes prepared from control and diabetic adipocytes exposed to the drug. Adipocytes from this model of diabetes are known to have a decreased cellular content of glucose transporters. The concentration of glucose transporters was decreased by 31% in plasma membranes from insulin-treated diabetic cells. There were corresponding decreases in diabetic microsomal and total membrane fractions. There was also a 40% decrease in the translocation of transporters from the microsomes to the plasma membrane in response to insulin in diabetic cells. Glyburide exposure increased the concentration of transporters in plasmamembranes from insulin-treated control and diabetic cells by 18 and 33%, respectively. Glyburide exposure also increased the concentration of glucose transporters in total adipocyte membrane preparations from diabetic but not control animals. Glyburide potentiates insulin-stimulated glucose transport in both control and diabetic adipocytes. In control cells, this effect is due to an increase in the efficiency of the translocation process. In diabetic cells, both cellular transporter content and the translocation process are increased by glyburide.