EFFECTS OF ORAL VANADYL TREATMENT ON DIABETES-INDUCED ALTERATIONS IN THE HEART GLUT-4 TRANSPORTER

Vanadyl sulfate was administered orally during a 10-week trial period to streptozotocin-diabetic and control male rats to test the hypothesi s that chronic vanadyl supplementation would prevent the decline in ca rdiac muscle cell glucose transporter protein (GLUT-4) that otherwise manifests in conjunction with insulin deficiency. Isolated cardiac myo cytes and cardiac sarcolemmal vesicles were prepared from heart tissue of rats that had been maintained on the following regimens: untreated control, oral vanadyl-supplemented control (0.6 mg/ml), untreated dia betic (streptozotocin-induced; 60 mg/kg), and vanadyl-supplemented dia betic. Myocytes isolated from untreated diabetic rat hearts had decrea sed rates of glucose oxidation. Chronic, oral administration of vanady l to diabetic rats maintained glucose oxidation rates of cardiac myocy tes at control levels. Immunoblot analyses revealed that total cardiac myocyte and sarcolemmal GLUT-4 glucose transporter protein levels wer e significantly lower in the diabetic group relative to control. Vanad yl treatment of diabetic rats produced a normalization of both sarcole mmal GLUT-4 and total cardiac myocyte levels towards control levels. T he reduction of GLUT-4 mRNA levels seen with untreated diabetes was al so completely prevented with vanadyl treatment, These results demonstr ate that chronic-oral vanadyl sulfate supplementation limits the decli ne in glucose oxidative capacity of cardiac myocytes that otherwise ma nifests in the untreated diabetic state. This action of vanadyl may oc cur via a mechanism that is linked to the preservation of sarcolemmal GLUT-4 protein levels. (C) 1997 Academic Press Limited.