Summary
The in vivo kinetic of removal of3H asialo-orosomucoid from plasma was investigated in control and streptozotocin-diabetic rats after intravenous injection of 1 mg of asialo-orosomucoid/100 g body wt. Michaelis-Menten kinetics of disappearance were observed. In diabetic rats the maximal rate (Vmax) of disappearance of3H asialo-orosomucoid was decreased by 30% with no modification of Michaelis constant. Since no accumulation of desialylated orosomucoid in the circulation was observed, the slower rate of removal of3H asialo-orosomucoid was attributed to a decrease in the number of hepatic asialoglycoprotein receptors which are largely involved in the catabolism of asialoglycoproteins. Our estimate on in vivo maximal rates was 10- to 20-fold greater than our previous in vitro estimate of the maximal rate of endocytosis. In contrast, the values of the Michaelis constant obtained in vivo and in vitro were very similar.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ashwell G, Morell AG (1974) The role of surface carbohydrates in the hepatic recognition and transport of circulating glycoproteins. Adv Enzymol 41: 99–128
Schwartz AL (1985) The hepatic asialoglycoprotein receptor. CRC Crit Rev Biochem 16: 207–233
Dodeur M, Durand D, Dumont J, Durand G, Féger J, Agneray J (1982) Effects of streptozotocin-induced diabetes mellitus on the binding and uptake of asialo-orosomucoid by isolated hepatocytes from rats. Eur J Biochem 123: 383–387
Dodeur M, Coumoul S, Durand D, Durand G, Féger J, Agneray J (1983) Diabetes induced variation in hepatic binding protein. Biochem Biophys Res Comm 115: 82–86
Zeitlin PL, Hubbard AL (1982) Cell surface distribution and intracellular fate of asialoglycoproteins: a morphological and biochemical study of isolated rat hepatocytes and mono-layer cultures. J Cell Biol 92: 634–647
Mancini G, Carbonara AO, Heremans JF (1965) Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2: 235–254
Laurell CB (1966) Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies. Anal Biochem 15: 45–52
Biou D, Monnet D, Millet F, Féger J, Durand G (1984) An immunochemical procedure to evaluate the degree of desialylation of alpha, -glycoprotein in rat serum. J Immunol Methods 74: 267–271
Wilder RL, Yven CC, Subbarao B, Woods VL, Alexander CB, Mage RG (1979) Tritium radio-labelling of protein A and antibody to high specific activity: application to cell surface antigen radio-immunoassays. J Immunol Methods 28: 255–263
Skeiner LB, (1981) ELSFIT Users Manual. Division of Clinical Pharmacology, University of California, San Francisco
Gomeni R (1984) PHARM, an interactive graphic program for individual and population pharmacokinetic parameter estimation. Comput Biol Med 14: 25–34
Clarenburg R (1983) Asialoglycoprotein receptor is univolved in clearing intact glycoproteins from rat blood. Am J Physiol 244: G247-G253
Regoeczi E, Debanne MT, Hatton MWC, Koj A (1978) Elimination of asialofetuin and asialo-orosomucoid by the intact rat. Quantitative aspects of the hepatic clearance mechanism. Biochim Biophys Acta 541: 372–384
Dodeur M, Coumoul S, Scarmato P, Durand G, Féger J, Agneray J (1984) Asialo-orosomucoid degradation by normal and diabetic rat hepatocytes. Eur J Biochem 140: 577–581
Jonsson A, Wales JK (1976) Blood glycoprotein levels in diabetes mellitus. Diabetologia 12: 245–250
Guzdek A (1979) The influence of experimental diabetes on the serum and urinary glycopeptide compounds in rats. Endocrinology 74:316–322
Pardridge WM, Van Herle AJ, Naruse RT, Fierer G, Costin A (1981) In vivo quantification of receptor-mediated uptake of asialoglycoproteins by rat liver. J Biol Chem 258: 990–994
Chandramouli V, Williams S, Marshall JS, Carter JR (1977) Cell surface changes in diabetic rats. Studies of lectin binding to liver cell plasma membranes. Biochim Biophys Acta 465: 19–33
Nassar K, Cheng S, Levy D (1981) The effect of diabetes on hepatocyte plasma membrane fluidity and Concanavalin A-induced agglutination. Exp Cell Res 132: 99–104
Durand G, Dumont JP, Appel M, Durand D, Davy J, Féger J, Agneray J (1980) Effect of streptozotocin diabetes on sialic acid and glycoprotein binding of isolated hepatocytes. Horm Metab Res 12: 247–251
Jefferson LS (1980) Role of insulin in the regulation of protein synthesis. Diabetes 29: 487–496
Draznin B, Trowbridge M (1982) Inhibition of intracellular proteolysis by insulin in isolated rat hepatocytes. Possible role of internalized hormone. J Biol Chem 257: 11988–11993
Hutson NJ, Lloyd CE, Mortimore GE (1982) Degradation of intra and extrahepatic protein by livers of normal and diabetic mice: differential responses to starvation. Proc Natl Acad Sci USA 79: 1737–1741
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Appel, M., Potrat, P., Feger, J. et al. In vivo quantification of removal of asialo-orosomucoid from the circulation in anaesthetized streptozotocin-diabetic rats. Diabetologia 29, 383–387 (1986). https://doi.org/10.1007/BF00903349
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00903349