Role of disturbed metabolism of fat tissue cells in the pathogenesis of the diabetogenic effect of obesity in humans.

It is supposed that the excess of fatty tissue exerts a diabetogenic effect. In obese subjects changes in the reactivity of the enlarged adipocytes to insulin might play a significant role in the pathogenesis of diabetes. Using the method of Rodbell in our own modification the responses of isolated adipocytes obtained from 10 lean and 15 obese subjects to a) insulin, b) theophylline and c) insulin and theophylline jointly (metabolism of glucose and glycerol) were determined. The dose-effect relationship curve was plotted against the effect of glucose utilization caused by increasing concentrations of insulin in the suspensions of adipocytes of lean and obese subjects. In adipocyte donors insulin sensitivity was also determined by Himsworth's test. It was found that adipocytes of 15 subjects with hyperthrophic obesity showed a significantly decreased effect of insulin regulating glucose utilization and glycerol release. They maintained a normal pattern of response to theophylline. The curve of relationship between insulin concentration in the incubation medium and its effect on glucose utilization by the adipocytes was changed. The adipocytes of these donors were relatively refractory to insulin in vivo as determined by the test of Himsworth. The cause of these disturbances may lie in the changed function of insulin receptors in the enlarged adipocytes. The observed disturbances may play a significant role in the pathophysiology of the diabetogenic effect of obesity.