Cellular basis of insulin resistance in chronic uremia

To define the cellular alterations responsible for insulin resistance during uremia, we studied insulin action in adipocytes isolated from rats 2 wk after 75% partial nephrectomy. Insulin binding to fat cells and purified liver plasma membranes prepared from uremic rats was unaltered. In contrast, hexose transport was significantly decreased, with and without insulin, in the fat cells from the uremic animals. The concentration of insulin that elicited half-maximal response was not altered. Glucose utilization was reduced in the absence or presence of insulin by partial nephrectomy. The stimulation of hexose transport and glucose metabolism by the insulin mimickers, hydrogen peroxide and vitamin K5, were also inhibited. Hexose transport activity in adipocytes obtained from uremic rats was no longer decreased when pieces of fat tissue were cultured for 20 h. Finally, hexose transport was reduced in the cells isolated from normal adipose tissue that was preincubated for 3 h with uremic serum, but insulin binding was not different than control. Thus, insulin resistance associated with uremia may be primarily accounted for by altered postreceptor events that appear to result from a circulating factor(s).