Insulin resistance in the aged: the role of the peripheral insulin receptors.

In the healthy subject, glucose tolerance tends to decrease with age due to impaired insulin secretion and/or decreased peripheral insulin activity. An oral glucose (100 g) tolerance test was performed on 12 aged (70 +/- 4 yr) and 8 young (32 +/- 7 yr) subjects; these subjects underwent laparatomy for cholecystectomy or the management of abdominal diseases. Subcutaneous adipose tissue was removed during surgery and fat cells, prepared according to a personal modification of Rodbell's method, were incubated in a medium containing monoiodo- and cold insulin to evaluate insulin binding and affinity constants. The results of the tolerance test pointed to an insulin resistant state i.e., impaired glucose tolerance coupled with normal plasma insulin, as previously shown also by us using other methods in the aged subject. The binding study demonstrates a distinct insulin receptor decrease in fat cells from the older subjects (185,000 +/- 19,200 as opposed to 310,000 +/- 12,000), without any change in affinity constants. The result indicates that insulin resistance in the aged may be attributed at least in part to a reduction in the number of insulin receptors on the target cells. This could be a consequence of aging itself, as proposed by other workers in the case of old fat rats.