Effect of Fasting on Insulin Receptor Binding and Insulin Action in Different Human Subcutaneous Fat Depots*

The possible existence of regional variations in fasting-mediated changes on insulin action an human adipose tissue was investigated in vitro. Subcutaneous adipose tissue was obtained from the femoral, abdominal, and gluteal areas of obese but otherwise normal subjects (16 women and 7 men) before and after 7 days of total fasting. Specific insulin receptor binding to isolated fat cells was similar in femoral and abdominal adipose tissues before and after fasting. However, the latter condition was associated with a significant increase in insulin receptor binding at low hormone concentrations (less than 2 nmol/liter) in gluteal adipocytes. Insulin stimulated glucose oxidation in a dose-dependent way in all 3 adipose regions before fasting. In the femoral and gluteal sites after fasting, the maximum insulin effect was significantly decreased, but a dose-dependent insulin effect was still present, and there was no change in insulin sensitivity. However, abdominal adipose tissue after fasting was completely unresponsive to insulin stimulation when the hormone was added in increasing concentrations up to 80 nmol/liter. The results in fasting women were similar to those in the whole study group. In conclusion, there appear to be marked regional variations in fasting-mediated changes in insulin action on glucose metabolism in human adipose tissue. Alterations at the postreceptor level which lead to insulin resistance appear to be of greater importance than the counteracting receptor changes.