Asialoorosomucoid degradation by normal and diabetic rat hepatocytes

Using high concentrations of extracellular [3H]asialoorosomucoid we obtained the steady-state level of [3H]asialoorosomucoid endocytosis by isolated hepatocytes from normal and streptozotocin diabetic rats. At the steady-state of the overall reaction, the intracellular amount of [3H]asialoorosomucoid did not change with time, the apparent overall rate of [3H]asialoorosomucoid degradation was close to that of [3H]asialoorosomucoid internalization, in both normal and diabetic rat hepatocytes. Although in diabetic cells the intracellular amount of [3H]asialoorosomucoid was about three-times lower than in normal cells, the same fraction of intracellular asialoorosomucoid was degraded per time interval by both normal and diabetic cells. The apparent first-order rate constant of steady-state degradation was about 0.011 min-1 for both normal and diabetic cells. In diabetic rat hepatocytes, the decrease of the clearance of serum asialoglycoproteins was directly correlated to the variation of cell surface receptor number, without any modification of internalization and degradation steps.