The mechanism of insulin-resistant glucose-transport activity in enlarged aged adipocytes was examined. Glucose-transport activity was assessed by measuring 3-O-methylglucose transport and the concentration of HepG2 erythrocyte/glucose transporter (GLUT1), and the muscle/adipose tissue transporter (GLUT4) was estimated by immunoblotting. Basal glucose-transport activity increased 6.3-fold/cell but remained constant per unit cellular surface area due to cell enlargement. Maximal insulin-stimulated transport activity remained constant per cell but decreased per unit cellular surface area. On a per protein basis, GLUT1 and GLUT4 from aged rats decreased to ∼60 and 10% of those from young rats, respectively. However, when the protein content of each fraction and the recoveries of marker enzymes were used for estimating the amount of transporters in intact adipocytes, the amount of GLUT1 per cell remained relatively constant, whereas that of GLUT4 decreased. In basal cells from young rats, 31% of the total GLUT1 per cell was located in the plasma membrane, whereas in those from aged rats, 63% was located in the plasma membrane. Thus, in comparing basal adipocytes from aged rats with those from young rats, GLUT1 per cell in the plasma membrane increased 2.8-fold, but this increase was less than that of transport activity (6.3-fold). In basal cells from young rats, 8% of the total GLUT4 was located in the plasma membrane, and a 4.5-fold increase was observed with insulin treatment, but the amount of GLUT4 in each fraction from aged rats markedly decreased. These findings suggest that the dramatic decrease of GLUT4 is a major cause of decreased insulin-stimulated glucose uptake and that GLUT1 located in the plasma membrane plays a part in maintaining basal glucose-transport activity.

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