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.