With the identification of two different
glucose transporter species in adipose cells it is crucial to determine the role of these transporters in the alterations in
glucose transport activity associated with different metabolic and nutritional states. In the present study we assess levels of expression of Glut 1 and Glut 4 transporters and basal and
insulin-stimulated
glucose transport activity in adipocytes from Sprague-Dawley rats fed standard chow (control), combined liquid diet and standard chow (overfed), high fat diet, or energy-restricted diet for 7 weeks. High fat feeding was associated with relative
postprandial hypoglycemia (P less than 0.05) and hypoinsulinemia (P less than 0.05). Although the high fat fed animals had lower
body weights (P less than 0.05) than control rats, their body compositions showed
obesity, with 36% heavier epididymal fat pads (P less than 0.05) and a 47% increase in adipocyte volume (P less than 0.05). Fat feeding caused a 78% reduction in
insulin-stimulated
glucose transport per adipocyte (P less than 0.05). In parallel we found 92% and 94% reductions in
Glut 4 protein and
mRNA per adipocyte, respectively, (P less than 0.01) in fat-fed rats. Substantial reductions were also seen in
Glut 1 protein and
mRNA per fat cell in the same rats (62% and 76%, respectively; P less than 0.05). However, the changes in Glut 1 expression were of the same magnitude as changes in the cytoskeletal
protein beta-actin, reflecting a decreased expression of several
proteins in this nutritional state. Even though overfeeding and energy restriction brought about opposite changes in adiposity, no significant alterations were demonstrated in
glucose transport rate or
glucose transporter expression. The impaired
insulin-stimulated
glucose transport in adipose cells from high fat-fed rats occurs in the presence of a dramatic decrease in the expression of the major
insulin-responsive glucose transporter (Glut 4). The reduced gene expression may be caused by chronic hypoinsulinemia and may contribute to the
insulin resistance observed in this state.