Insulin binding and removal by livers of genetically obese rats

Livers from 9-10-wk-old genetically obese and hyperinsulinemic (fa/fa) rats contained more DNA, proteins, and lipids than livers of age-matched controls. Actually, the increase in liver mass of fa/fa rats was mainly due to an increased cell number. On perfusion with insulin (1.75-16 nM), livers of obese fa/fa rats removed 35-40% less insulin per gram tissue than control livers. When calculated on a per organ basis, removal capacity was, however, similar in livers of control and obese fa/fa rats. The binding of 125I-insulin to as well as the insulin removal by isolated hepatocytes was also assessed. Contrary to previous unexpected data in which the downregulation of insulin receptors by hyperinsulinemia was reported not to prevail in hepatocytes from obese fa/fa rats, it was found that the binding capacity of hepatocytes from fa/fa rats was decreased by 45% without alteration of the binding affinity. Moreover, in hepatocytes from obese fa/fa rats, both binding and removal of insulin were lowered to an analogous extent. It is concluded that livers of obese fa/fa rats behave, with regard to insulin binding and removal, as those of other hyperinsulinemic obese animals.