Impaired glucose transport in skeletal muscle but normal GLUT-4 tissue distribution in glucose-infused rats.
This study was undertaken to determine if glucose toxicity in normal rats caused decreased whole body insulin-stimulated glucose disposal and in vivo impaired muscle glucose transport and, if so, whether it was mediated by changes in GLUT-4 content or tissue distribution. Rats were infused with 50% dextrose for 48 h after which they were clamped and injected with 2-deoxy-D-[3H]glucose. Hindlimb muscles were removed for measurement of uptake of radioactivity (glucose transport) and GLUT-4 levels in total, plasma and internal membrane fractions. Dextrose infusions caused significant hyperglycemia [15.5 +/- 1.4 vs. 6.7 +/- 0.3 (SE) mM], hyperinsulinemia [678 +/- 108 vs. 168 +/- 42 (SE) pM], and depressed insulin-mediated whole body glucose disposal [12.8 +/- 2.0 vs. 47.0 +/- 10.6 (SE) mg glucose.kg-1.min-1.pmol insulin-1.1(-1) x 10(3)]. Muscle glucose transport (ng.min-1.mg tissue-1) was significantly decreased in biceps (4.0 +/- 0.6 vs. 13.4 +/- 2.5), gastrocnemius (4.6 +/- 1.1 vs. 12.9 +/- 2.2), and plantaris (5.5 +/- 0.7 vs. 17.5 +/- 3.6) muscles compared with saline-infused rats. The difference in the soleus muscle (13.2 +/- 1.6 vs. 19.4 +/- 2.7) did not quite reach statistical significance. There were no differences in total, plasma, or internal membrane GLUT-4 content between the two groups. It is concluded that glucose toxicity causes impaired insulin-stimulated glucose transport, probably due to decreased activity of GLUT-4.
Davidson
M B
MB
Department of Medicine, Cedars-Sinai Medical Center, University of California at Los Angeles 90048.
Bouch
C
C
Venkatesan
N
N
Karjala
R G
RG
D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D005947:Glucose / Q000378:metabolism* / Q000633:toxicity; D051275:Glucose Transporter Type 4; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000032:analysis*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D009597:4-Nitrophenylphosphatase; D005947:Glucose