Summary
Six to 12 h after IP injection of 400 mg/kg of D-galactosamine in rats a 5-fold increase in plasma insulin was observed. In addition, impaired glucose assimilation was present after an IV load in spite of unchanged fasting glucose levels. In streptozotocin-diabetic rats (100 mg/kg IV) plasma insulin remained diminished 12 h after induction of D-galactosamine hepatitis. Under identical conditions of preparation and incubation, the liver plasma membranes of D-galactosamine-treated rats, in both normal and diabetic states, bound only 40–60% as much insulin per mg of membrane protein as those of the control rats. Scatchard analysis suggested that this was due to a decrease in the number of receptor sites in the membranes of the D-galactosamine-injected rats. No difference in the insulin degrading capacity and in insulin-receptor dissociation of the plasma membranes between control and D-galactosaminetreated groups was found. These data suggest that a reduction in the number of hepatic insulin receptors in galactosamine hepatitis can lead to insulin resistance and hyperinsulinaemia.
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Kahn, C.R., Roth, J.: Insulin receptors in disease states. In: Hormone-receptor interaction: molecular aspects. Levey, G.S. (Ed.), pp. 1–29. New York, Basel: Marcel Dekker, Inc. 1976
Freychet, P.: Recent studies on insulin-receptor interactions. Isr. J. Med. Sci.11, 679–686 (1976)
Kahn, C.R., Megyesi, K., Bar, R.S., Eastman, R.C., Flier, J.S.: Receptors for peptide hormones. New insights into the pathophysiology of disease states in man. Ann. Intern. Med.86, 205–219 (1977)
DeFronzo, R.A., Soman, V., Sherwin, R.S., Hendler, R., Felig, Ph.: Insulin binding to monocytes and insulin action in human obesity, starvation, and refeeding. J. Clin. Invest.62, 204–213 (1978)
Hepp, K.D., Langley, J., v. Funcke, J., Renner, R., Kemmler, W.: Increased insulin binding capacity of liver membranes from diabetic Chinese hamsters. Nature258, 154 (1975)
Davidson, M.B., Kaplan, S.A.: Increased insulin binding by hepatic plasma membranes from diabetic rats. J. Clin. Invest.59, 22–30 (1977)
Beck-Nielsen, H., Pedersen, O.: Insulin receptors on monocytes of young healthy persons correlated with glucose tolerance and insulin sensitivity. Diabetologia14, 159–163 (1978)
Kobayashy, M., Olefsky, J.M.: Effect of experimental hyperinsulinemia on insulin binding and glucose transport in isolated rat adipocytes. Am. J. Physiol.235, 53–62 (1978)
Keppler, D., Lesch, R., Reutter, W., Decker, K.: Experimental hepatitis induced by D-galactosamine. Exp. Mol. Pathol.9, 279–290 (1968)
Bachmann, W., Harms, E., Hassels, B., Henninger, H., Reutter, W.: Studies on rat liver plasma membrane. Altered protein and phospholipid metabolism after injection of D-galactosamine. Biochem. J.166, 455–462 (1977)
Reutter, W., Keppler, D., Lesch, R., Decker, K.: Zum Gly-koproteidstoffwechsel bei der Galaktosamin-induzierten Hepatitis. Verh. Dtsch. Ges. Inn. Med.75, 363–365 (1969)
Record, C.O., Alberti, K.G.M.M.: Glucose tolerance and blood metabolite changes in galactosamine hepatitis and obstructive jaundice in the rat. Eur. J. Clin. Invest.3, 130–135 (1973)
Jacobs, S., Shechter, Y., Bisseil, K., Cuatrecasas, P.: Purification and properties of insulin receptors from rat liver membranes. Biochem. Biophys. Res. Commun.77, 981–988 (1977)
Cuatrecasas, P., Illiano, G.: Membrane sialic acid and the mechanism of insulin action in adipose tissue cells: Effects of digestion with neuraminidase. J. Biol. Chem.246, 4938–4946 (1971)
Cuatrecasas, P., Tell, G.P.E.: Insulin-like activity of concanavalin A and wheat germ agglutinin — Direct interaction with insulin receptors. Proc. Natl. Acad. Sci. USA70, 485–489 (1973)
Schmidt, F.: Die enzymatische Bestimmung von Glucose und Fructose nebeneinander. Klin. Wochenschr.39, 1244–1247 (1961)
Bergmeyer, H.U.: Glutamat-Oxalacetat-Transaminase. In: Methoden der enzymatischen Analyse. Bergmeyer, H.U. (Ed.), pp. 769–755. Weinheim/Bergstr.: Verlag Chemie 1974
Herbert, V., Lau, K.S., Gottlieb, C.W., Bleicher, S.: Coated charcoal immunoassay of insulin. J. Clin. Endocrinol.25, 1375–1384 (1965)
Yalow, R.S., Berson, S.A.: Immunoassay of endogenous plasma insulin in man. J. Clin. Invest.39, 1157–1175 (1960)
Neville, D.M.: The isolation of a cell membrane fraction from rat liver. J. Biophys. Biochem. Cytol.8, 413–422 (1960)
Ray, T.K.: A modified method for the isolation of the plasma membrane from rat liver. Biochim. Biophys. Acta196, 1–9 (1970)
Mchell, R.H., Hawthorne, F.N.: The site of diphosphoinositide synthesis in the rat liver. Biochem. Biophys. Res. Commun.21, 333–338 (1965)
Emmelot, P., Bos, C.J.: Studies on plasma membranes. III. Mg2+-ATPase (Na+-K+-Mg2+)-ATPase and 5′-nucleotidase activity of plasma membranes isolated from rat liver. Biochim. Biophys. Acta120, 369–382 (1966)
Emmelot, P., Bos, C.J., Benedetti, E.L., Rümke, P.: Studies on plasma membranes. I. Chemical composition and enzyme content of plasma membranes isolated from rat liver. Biochim. Biophys. Acta90, 126–145 (1964)
Pennington, F.: Biochemistry of dystrophic muscle. Mitochondrial succinate-tetrazolium reductase and adenosine triphosphatase. Biochem. J.80, 649–654 (1961)
DeDuve, C., Pressmann, B.C., Gianetto, R., Wattiaux, R., Appelmans, O.O.: Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat liver tissue. Biochem. J.60, 604–617 (1955)
Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.L.: Protein measurement with the folin phenol reagent. J. Biol. Chem.193, 265–275 (1951)
Kemmler, W., Renner, R., Zynamon, A., Hepp, K.D.: Interaction between insulins and liver membrane receptors of guinea pig, beef and chicken. Biochim. Biophys. Acta543, 349–356 (1978)
Scatchard, G.: The attractions of proteins for small molecules and ions. Ann. N. Y. Acad. Sci.51, 660–675 (1949)
Chandramouli, V., Carter, Jr., J.R.: Cell membrane changes in chronically diabetic rats. Diabetes24, 257–262 (1975)
Kremer, G.J., Atzpodien, W., Jacobi, H., Friederichs, U., Friederichs, M.: Glucose and insulin tolerance studies in viral hepatitis. Inn. Med.3, 267–276 (1976)
Record, C.O., Alberti, K.G.M.M., Williamson, D.H., Wright, R.: Glucose tolerance and metabolic changes in human viral hepatitis. Clin. Sci. Mol. Med.45, 677–690 (1973)
Medline, A., Schaffner, F., Popper, H.: Ultrastructural features in galactosamine-induced hepatitis. Exp. Mol. Pathol.12, 201–211 (1970)
Sabesin, S.M., Koff, R.S.: D-galactosamine hepatotoxicity. IV. Further studies of the pathogenesis of fatty liver. Exp. Mol. Pathol.24, 424–434 (1976)
Shinozuka, H., Farber, J.L., Konishi, Y., Anukarahanonta, T.: D-galactosamine and acute liver cell injury. Fed. Proc.32, 1516–1526 (1973)
Michell, R.H.: Inositol phospholipids and cell surface receptor function. Biochim. Biophys. Acta415, 81–147 (1975)
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Bachmann, W., Haslbeck, M., Böttger, I. et al. Reduced insulin binding to hepatic plasma membranes in D-galactosamine-treated rats. Diabetologia 17, 101–109 (1979). https://doi.org/10.1007/BF01222210
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DOI: https://doi.org/10.1007/BF01222210