Site Differences in Insulin Receptor Binding and Insulin Action in Subcutaneous Fat of Obese Females*

Abstract

Regional differences in insulin-induced sc adipose tissue metabolism in 7 weight-stable obese women were investigated. Insulin receptor binding to isolated fat cells and the effects of insulin on glucose oxidation and lipolysis in adipose tissue segments obtained from abdominal and femoral regions were determined. The mean dose-response relationships for the antilipolytic effect of insulin were almost identical in both regions; the half-maximum effect (ED₅₀) was obtained with 100 μU/ml, and the maximum effect (responsiveness) was a decrease of about 7 μmol glycerol/10⁷ cells·2 h. The mean insulin dose-response curves for glucose oxidation differed; the ED₅₀ was 100 μU/ml in femoral and 300 μU/ml in abdominal adipose tissue (P < 0.01), and responsiveness was enhanced 2-fold in femoral fat (P < 0.01). Insulin receptor number was higher in femoral than in abdominal adipocytes (600,000 and 250,000 sites/cell, respectively; P < 0.01). However, the apparent insulin receptor affinity was increased 2- to 3-fold in abdominal fat cells. The ED₅₀ for insulin stimulation of glucose utilization occurred at a higher level of receptor occupancy in abdominal than in femoral fat. Thus, significant regional differences in insulin binding and insulin action were found in sc fat depots in obese women. Differences at the postreceptor rather than at the receptor level are probably responsible for the enhanced insulin-induced glucose utilization in femoral fat.