Insulin resistance in uremia: an in vivo and in vitro study

Insulin-mediated glucose metabolism was examined in vivo and in vitro in a chronically uremic (4-week) rat model established by a 90% nephrectomy. Using the euglycemic insulin clamp technique, uremic rats demonstrated a 28% reduction (P less than .01) in total body glucose disposal compared with pair-fed controls. Suppression of hepatic glucose production by insulin was not impaired. The ability of insulin to promote glycogen synthesis by the soleus muscle in vitro was normal in uremic rats. In contrast, the ability of insulin to enhance both glycolysis and glucose oxidation by the soleus muscle was significantly reduced (P less than .01) in uremic rats. These results provide evidence that at least two intracellular metabolic defects, ie, in the glycolytic and glucose oxidative pathways, contribute to the insulin resistance of chronic uremia.