
<ArticleTitle>Altered <prot>GLUT1</prot> and <prot>GLUT3</prot> gene expression and subcellular redistribution of <prot>GLUT4</prot>: protein in muscle from patients with acanthosis nigricans and severe <prot>insulin</prot> resistance.</ArticleTitle>
<AbstractText>Multiple isoforms of glucose transporters are found in muscle, the tissue that normally accounts for 85% of <prot>insulin</prot>-stimulated glucose uptake. Glucose uptake into muscle cells in the fasting state is mediated primarily by <prot>GLUT1</prot> and <prot>GLUT3</prot> glucose transporters, whereas postprandial (<prot>insulin</prot>-stimulated) and exercise-related increments in muscle glucose uptake are mediated primarily by <prot>GLUT4</prot>. 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 <prot>insulin</prot> resistance and acanthosis nigricans. Both <prot>GLUT4</prot> total protein and mRNA were normal in the <prot>insulin</prot>-resistant subjects. Muscle <prot>GLUT3</prot> protein and mRNA were lower than controls by 62% and 71%, respectively. <prot>GLUT1</prot> mRNA was twice normal, whereas <prot>GLUT1</prot> protein content was not significantly increased. <prot>GLUT4</prot> protein was markedly redistributed to the muscle plasma membrane in subjects with severe <prot>insulin</prot> resistance compared with normals (92% v 40% <prot>GLUT4</prot> in plasma membrane-enriched fractions, P &#60;.001), whereas the percentage of <prot>GLUT1</prot> and <prot>GLUT3</prot> protein found in the plasma membrane-enriched fractions was not different from controls. These data document differences in the expression of genes for <prot>GLUT1</prot> and <prot>GLUT3</prot> in muscle from normal and <prot>insulin</prot>-resistant subjects. Further, <prot>insulin</prot> resistance with fasting hyperinsulinemia was associated with a redistribution of <prot>GLUT4</prot> to the muscle cell surface with no change in total <prot>GLUT4</prot> protein. These data suggest that glucose transporter gene expression and their basal distribution in human muscle are related to <prot>insulin</prot> resistance and could be determinants of whole body <prot>insulin</prot> responsiveness.</AbstractText>
