The role of the glucose transport system in the postreceptor defect in insulin action associated with human aging.

In an attempt to elucidate the cellular mechanisms of the insulin resistance associated with aging, insulin-mediated glucose transport was studied in isolated adipocytes obtained from 14 elderly subjects (mean age +/- SE, 69 +/- 2 yr) and 11 nonelderly (40 +/- 4 yr) subjects using the nonmetabolized glucose analogue 3-O-methylglucose. In elderly subjects with normal oral glucose tolerance tests, maximal insulin-stimulated glucose transport was reduced compared to nonelderly control levels [1.26 +/- 0.17 (+/- SE) vs. 1.96 +/- 0.26 pmol/2 X 10(5) cells X 15 sec; P less than 0.025). Elderly subjects with nondiagnostic oral glucose tolerance tests had more marked reductions in basal, submaximal, and maximal stimulated rates of glucose transport compared to the nonelderly group. The elderly group with the greatest decrease in in vitro glucose transport also had the greatest decrease in in vivo insulin-stimulated glucose disposal, whereas the elderly subjects with the mildest in vitro defect also had the smallest reduction in in vivo glucose disposal. A significant positive relationship existed between the maximal rate of in vitro glucose transport and the maximal rate of in vivo glucose disposal in the various subjects (Spearman rank correlation coefficient = 0.54; P less than 0.05). We conclude that aging is associated with a significant defect in the glucose transport system in isolated adipocytes, which may account for the post-receptor defect in in vivo insulin action in aging.