Effects of obesity, hyperinsulinemia, and glucose intolerance on insulin action in adipose tissue of sixty-year-old men.

The relative effects of obesity alone, and in combination with fasting hyperinsulinemia and glucose intolerance, on the peripheral action of insulin in adipose tissue were investigated in twenty-four 60-yr-old men, who had been followed for 10 yr. They were divided into four groups of six subjects each on the basis of the following criteria: (1) normal body weight, normal fasting insulin level, and normal glucose tolerance; (2) moderate obesity, normal fasting insulin level, and normal glucose tolerance; (3) moderate obesity, fasting hyperinsulinemia, and normal glucose tolerance; and (4) moderate obesity, fasting hyperinsulinemia, and newly developed, moderate, untreated fasting hyperglycemia and/or glucose intolerance (i.e., mild type II diabetes mellitus). Specific adipocyte insulin binding and the effects of the hormone on adipose tissue lipolysis and glucose oxidation were determined. Insulin receptor binding per cell and per cell surface area were similar in all four groups. Regarding antilipolysis, the insulin sensitivity was the same in all groups and the maximum effect was significantly increased in the three obese groups, as compared with the normal-weight control group. In groups 1-3, insulin stimulated adipose tissue glucose oxidation in a dose-dependent way, and the sensitivity and responsiveness to insulin were comparable. In contrast, in the obese glucose-intolerant subjects (4) there was no significant effect of insulin on glucose oxidation when the hormone was added in increasing concentrations of less than or equal to 35 nmol/L. The basal glucose oxidation was similar in all four study groups. The in vivo insulin tolerance was gradually reduced in groups 2-4, as compared with the normal-weight control group.(ABSTRACT TRUNCATED AT 250 WORDS)