Abstract
The ability of the liver to metabolise 125I-insulin was studied in regard to a varying insulin level within a physiological concentration, age and fasted state in the cyclically perfused rat liver. High performance liquid chromatography was used to measure 125I-insulin and its radioactive degradation products. Insulin disappearance from perfusates followed first-order kinetics in all experiments. The half life was 10.7±1.1 min and clearance was 6.5±0.6 ml/min/liver at 100 μU/ml 125I-insulin level and these remained almost unchanged at 200, 400 and 800 μU/ml. In 7-, 12- and 21-old-day rats, clearances per g wet liver (0.39±0.09, 0.34±0.06 and 0.33±0.05 ml/ min/g wet liver) was significantly smaller than that of adult rats at 100 μU/ml ; however, there existed no significant difference between 30-day-old rats and 8-9-week-old rats. Clearances per liver increased after becoming 12-day-old with an increasing liver weight. Clearances in adult and 21-day-old rats having fasted for 96 hours were significantly reduced and the half life was 2.2 times longer as in each control group. Radioactive degradation products were free-125I 125I-Tyr and substances of three different molecular weights (78, 000, 48, 000 and 26, 000). The amount of these degradation products changed with insulin clearance : the amount of degradation products was equal to that of reduced 125I-insulin in perfusates. These results suggest that metabolic states, i.e. age and fasting, rather than insulin concentration influence removal and degradation of insulin by the liver.
