Altered GLUT1 and GLUT3 gene expression and subcellular redistribution of GLUT4: protein in muscle from patients with acanthosis nigricans and severe insulin resistance.
Multiple isoforms of glucose transporters are found in muscle, the tissue that normally accounts for 85% of insulin-stimulated glucose uptake. Glucose uptake into muscle cells in the fasting state is mediated primarily by GLUT1 and GLUT3 glucose transporters, whereas postprandial (insulin-stimulated) and exercise-related increments in muscle glucose uptake are mediated primarily by GLUT4. To determine if glucose transporters are abnormally expressed in muscle from insulin-resistant subjects, muscle samples were obtained from 10 normal subjects and 6 obese, nondiabetic subjects with severe insulin resistance and acanthosis nigricans. Both GLUT4 total protein and mRNA were normal in the insulin-resistant subjects. Muscle GLUT3 protein and mRNA were lower than controls by 62% and 71%, respectively. GLUT1 mRNA was twice normal, whereas GLUT1 protein content was not significantly increased. GLUT4 protein was markedly redistributed to the muscle plasma membrane in subjects with severe insulin resistance compared with normals (92% v 40% GLUT4 in plasma membrane-enriched fractions, P <.001), whereas the percentage of GLUT1 and GLUT3 protein found in the plasma membrane-enriched fractions was not different from controls. These data document differences in the expression of genes for GLUT1 and GLUT3 in muscle from normal and insulin-resistant subjects. Further, insulin resistance with fasting hyperinsulinemia was associated with a redistribution of GLUT4 to the muscle cell surface with no change in total GLUT4 protein. These data suggest that glucose transporter gene expression and their basal distribution in human muscle are related to insulin resistance and could be determinants of whole body insulin responsiveness.
Stuart
C A
CA
Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, TX, USA.
Wen
G
G
Williamson
M E
ME
Jiang
J
J
Gilkison
C R
CR
Blackwell
S J
SJ
Nagamani
M
M
Ferrando
A A
AA
D000052:Acanthosis Nigricans / Q000378:metabolism*; D000328:Adult; D005260:Female; D005786:Gene Expression Regulation; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism*; D009419:Nerve Tissue Proteins
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C495692:SLC2A4 protein, human