The effects of diabetes and insulin on glycoprotein metabolism by rat liver

Abstract

The hepatic metabolism of [125I]agalactoorosomucoid [( 125I]AGOR) was studied in normal and streptozotocin-induced diabetic rats. The blood clearance, hepatic transport time and rate of catabolism of [125I]AGOR were calculated from data of the blood [125I]AGOR disappearance rates and the appearance in blood of acid-soluble catabolites. In control rats the blood clearance of [125I]AGOR was rapid (8.7 +/- 0.6 ml/min) and the hepatic transport time of the ligand was 12.8 +/- 0.7 min. Insulin prolonged the hepatic transport time (18.1 +/- 1.9 min) and depressed ligand catabolism. Chloroquine had similar effects. Diabetes impaired hepatic [125I]AGOR uptake as judged by the prolonged blood clearance rate and depressed ligand catabolism but did not alter ligand transport time. The measured parameters returned to normal when diabetic animals were rendered acutely normoglycaemic. Diabetic rats, in which implanted osmotic insulin pumps had maintained normoglycaemia for 3 days, cleared [125I]-AGOR from the blood more rapidly than controls. This effect appeared to be due to the lower blood glucose levels in this group. The experiments have shown the complexity of the effects of insulin and diabetes mellitus on the uptake and processing of a glycoprotein by the hepatic mannose receptor.