The influence of aging on the peripheral action of insulin was studied using subcutaneous adipose tissue from eight young (range 22–30 yr) and seven middle-aged (40–59 yr). healthy, normal-weight subjects. Insulin binding per cell was 50% lower in the older than in the younger group (P < 0.01), essentially owing to a decrease in the insulin receptor number. Concomitantly, insulin sensitivity, as reflected in the degree of antilipolysis and stimulation of glucose oxidation, was 10–20 times smaller in the older subjects (P < 0.01). Basal lipolysis and the maximum antilipolytic effect of insulin were similar in the two groups. The basal rate of glucose oxidation in the older subjects was less than one-half that for the younger group (P < 0.025), and the maximum level of insulin-induced glucose oxidation was lower by about 75% (P < 0.01). Age was significantly and negatively correlated with insulin receptor number (r = −0.81), basal production of 14Co2 (r = −0.73) and maximum level of insulin-induced glucose oxidation (r = −0.68). The decreases in the receptor number and insulin sensitivity were larger in early adulthood than in the elderly, while the decrease in insulin responsiveness was more uniform. It is concluded that aging is accompanied by impairment of the action of insulin on target cells, owing to alterations at both the receptor and the postreceptor levels. These mechanisms, and especially the postreceptor defect, may be essential factors in the development of relative glucose intolerance in the aged.

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