Effect of acute uremia on insulin removal by the isolated perfused rat liver and muscle

The effect of acute uremia on insulin removal by liver and muscle was investigated by measuring the extraction of porcine insulin during recycling perfusion of isolated liver and hindlimb from nephrectomized rats. Insulin removal by the liver was not affected by uremia, and hepatic extraction of insulin by normal and uremic livers averaged 38% at perfusate insulin concentrations ranging from 50 to 600 μU/ml. In contrast, insulin extraction by normal hindlimb averaged 13.4% at comparable insulin concentrations, and this was reduced to 4.3% as a result of acute uremia. A similar reduction in insulin extraction was noted when hindlimb from uremic animals was perfused with normal blood media or when normal hindlimb was perfused with uremic blood. These findings indicate that the efficiency of insulin removal by the liver is unaffected by uremia and is approximately threefold higher than that for hindlimb muscle. On the other hand, it is apparent that skeletal muscle, by virtue of its mass and relatively high blood flow, is also an important organ system for insulin removal. Furthermore, the data suggest that the 68% reduction in insulin extraction by hindlimb from uremic rats may contribute to the prolongation of insulin removal from plasma that is characteristic of patients with renal failure.