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 hypothesis that chronic vanadyl supplementation would prevent the decline in cardiac muscle cell glucose transporter protein (GLUT-4) that otherwise manifests in conjunction with insulin deficiency. Isolated cardiac myocytes 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 diabetic (streptozotocin-induced; 60 mg/kg), and vanadyl-supplemented diabetic. Myocytes isolated from untreated diabetic rat hearts had decreased rates of glucose oxidation. Chronic, oral administration of vanadyl to diabetic rats maintained glucose oxidation rates of cardiac myocytes at control levels. Immunoblot analyses revealed that total cardiac myocyte and sarcolemmal GLUT-4 glucose transporter protein levels were significantly lower in the diabetic group relative to control. Vanadyl treatment of diabetic rats produced a normalization of both sarcolemmal GLUT-4 and total cardiac myocyte levels towards control levels. The reduction of GLUT-4 mRNA levels seen with untreated diabetes was also completely prevented with vanadyl treatment. These results demonstrate that chronic-oral vanadyl sulfate supplementation limits the decline in glucose oxidative capacity of cardiac myocytes that otherwise manifests in the untreated diabetic state. This action of vanadyl may occur via a mechanism that is linked to the preservation of sarcolemmal GLUT-4 protein levels.
Kopp
S J
SJ
Department of Physiology, Midwestern University, Downers Grove, IL 60515, USA.
Daar
J
J
Paulson
D J
DJ
Romano
F D
FD
Laddaga
R
R
D009597:4-Nitrophenylphosphatase / Q000187:drug effects / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D051275:Glucose Transporter Type 4; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014638:Vanadates / Q000494:pharmacology*
D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C495694:Slc2a4 protein, rat; D014280:Triglycerides; D014638:Vanadates; D002784:Cholesterol; D009597:4-Nitrophenylphosphatase