Naunyn-Schmiedebergs Archiv für Pharmakologie

, Volume 266, Issue 1, pp 3–17 | Cite as

Wirkung eines Insulinmangels auf die Bilirubinausscheidung in der Galle

  • B. Müller-Oerlinghausen
  • G. Schinke


Bilirubin Diabetes Galle Glucuronide Leber 

Influence of insulin deficiency on the excretion of bilirubin in bile


The biliary excretion of bilirubin has been investigated in diabetic rats. Diabetes was induced by injection of anti-insulin-serum (AIS) or alloxan 13 hrs or 6 weeks, respectively before the experiment. The maximal transport capacity of the liver (Tm) was reduced in AIS-diabetic animals by 42%. The observed reduction of bilirubin secretion was smaller in alloxanized rats. The maximal bilirubin excretion rate of the perfused liver of diabetic animals was even more depressed than it was in the experiments with intact, anesthetized animals. Therefore, the observed effects can not be due to unspecific changes, such as an impairment of hepatic blood flow because of insulin deficiency. The uptake of unconjugated bilirubin was not inhibited in the perfused liver of diabetic rats. Thus, it is suggested that the reduced synthesis of UDP-glucuronic acid which has been found in former experimentsin vitro is responsible for the impaired bilirubin excretion. Accordingly, the elimination of bile pigment which had been infused in the conjugated form was found to be unchanged in AIS-diabetic rats. — The excretion of indocyanine green which is not metabolized in the liver was delayed, the Tm-value of this dye, however, was only slightly decreased in AIS-diabetic animals. Thus preliminary evidence suggests that lack of insulin might also affect the biliary excretion of compounds other than bilirubin.


Bile Bilirubin Diabetes Glucuronates Liver 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Acocella, G.: A symbiotic system for the study of the excretion of bile pigments in rats. In: I. A. D. Bouchier and B. H. Billing (Ed.): Bilirubin metabolism. Oxford-Edinburgh: Blackwell 1967.Google Scholar
  2. Arias, I. M.: Ethereal and N-linked ghicuronide formation by normal and Gunn rats in vitro and in vivo. Biochem. biophys. Res. Commun.6, 81 (1961).Google Scholar
  3. —: The excretion of conjugated bilirubin by the liver cell. Medicine (Baltimore)45, 513 (1966).Google Scholar
  4. Billing, B. H., Ali, M., Dunncliff, M.: C14-Bilirubin metabolism in obstructive jaundice. In: O. Wieland (Ed.): 6th Internat. Congr. Clin. Chem., Vol. 4. Basel: Karger 1968.Google Scholar
  5. Brauer, R. W.: Liver circulation and function. Physiol. Rev.43, 115 (1963).Google Scholar
  6. —: Hepatic blood supply and the secretion of bile. In: W. Taylor (Ed.): The biliary system. Oxford: Blaokwell 1965.Google Scholar
  7. Brown, A. K., Zuelzer, W. W.: Studies on the neonatal development of the glucuronide conjugating system. J. clin. Invest.37, 332 (1958).Google Scholar
  8. Creutzfeldt, W., Skutella, E., Moshagen, D., Kneer, P., Soling, H.-D.: Die Wirkung von N1Sulfanilyl-N2-butylcarbamid (Carbutamid) auf den Stoffwechsel der isoliert perfundierten Leber von normalen und alloxandiabetischen ketotischen Ratten. Diabetologia3, 9 (1967).Google Scholar
  9. Danysz, A., Wisniewski, K.: The influence of insulin on drag passage into the tissue. Arch. int. Pharmacodyn.158, 30 (1965).Google Scholar
  10. Dutton, G. J.: Comparison of glucuronide synthesis in developing mammalian and avian liver. Ann. N. Y. Acad. Sci.111, 259 (1963).Google Scholar
  11. Eckhardt, E. T., Plaa, G. L.: Role of biotransformation, biliary excretion and circulatory changes in chlorpromazine induced sulfobromophthalein retention. J. Pharmacol. exp. Ther.139, 383 (1963).Google Scholar
  12. Exton, J. A., Park, C. R.: Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused liver of rats. J. biol. Chem.242, 2622 (1967).Google Scholar
  13. Garay, E. A. R., Campa, J. P.: Bilirubin metabolism in experimental liver injury. J. Lab. clin. Med.72, 582 (1968).Google Scholar
  14. Grodsky, G.: Studies in the uptake and intrahepatic transport of H-bilirubin. In: Bouchier, I. A. D., and B. H. Billing (Ed.): Bilirubin metabolism. Oxford-Edinburgh: Blackwell 1967.Google Scholar
  15. Hargreaves, T.: Bilirubin, bromsulphthalein and indocyanine green excretion in bile. Quart. J. exp. Physiol.51, 184 (1966).Google Scholar
  16. Isselbacher, K. J., McCarthy, E. A.: Studies on bilirubin sulfate and other non-glucuronide conjugates of bilirubin. J. clin. Invest.38, 645 (1959).Google Scholar
  17. Jendrassik, L., Cleghorn, R.: Photometrische Bilirubinbestimmung. Biochem. Z.289, 1 (1937).Google Scholar
  18. Koss, F. W., Beisenherz, G.: Die choleretische Wirkung des 1-Phenyl-1-hydroxy-n-Pentans. Arzneimittel-Forsch.14, 191 (1964).Google Scholar
  19. Lester, R., Klein, P. D.: Biosynthesis of tritiated bilirubin and studies of its excretion in the rat. J. Lab. clin. Med.67, 1000 (1966).Google Scholar
  20. Maggiore, Q., Carter, M., Billing, B. H.: La diversa distribuzione della bilirubina libera e conjugata nel sangue e nel fegato. Boll. Soc. ital. Biol. sper.39, 945 (1963).Google Scholar
  21. Mortimore, G. E.: Effect of insulin on release of glucose and urea by isolated rat liver. Amer. J. Physiol.200, 699 (1963).Google Scholar
  22. Muller-Oerlinghausen, B.: Pharmakologische und hormonelle Beeinflussung der hepatisehen Glucuronidsynthese und der Bilirubinexkretion — unter besonderer Berücksichtigung des experimentellen Diabetes. Habil.-Schrift, Göttingen 1969.Google Scholar
  23. —: Über die gestörte Glucuronidsynthese in der Leber diabetischer Ratten. Naunyn-Schmiedebergs Arch. Pharmak.265, 372 (1970).Google Scholar
  24. —, Hasselblatt, A., Jahns, R.: Impaired hepatic synthesis of glucuronic acid conjugates in diabetic rats. Life Sci.6, 1529 (1967).Google Scholar
  25. Noir, B., Walz, A. T., de, Garay, E. R.: Studies on bilirubin sulfate in human bile. In: Bouchier, I. A. D., and B. H. Billing (Ed.): Bilirubin metabolism. Oxford-Edinburgh: Blackwell 1967.Google Scholar
  26. Roberts, R. J., Klaassen, C. D., Plaa, G. L.: Maximum biliary excretion of bilirubin and sulfobromophthalein during anesthesia-induced alteration of rectal temperature. Proc. Soc. exp. Biol. (N. Y.)125, 313 (1967).Google Scholar
  27. —, Plaa, G. L.: Effect of phenobarbital on the excretion of an exogenous bilirubin load. Biochem. Pharmaool.16, 827 (1967).Google Scholar
  28. Schellong, G.: Notwendigkeit und Problematik einer international einheitlichen Standardisierung der Methoden zur Bilirubinbestimmung. Dtsch. med. Wschr.88, 1145 (1963).Google Scholar
  29. Tisdale, M., Klabskin, G.: The significance of the direct-reacting fraction of serum bilirubin in haemolytic jaundice. Amer. J. Med.26, 214 (1959).Google Scholar
  30. Weinbren, K., Billing, B.: Hepatic clearance of bilirubin as an index of cellular function in the regenerating rat liver. Brit. J. exp. Path.37, 199 (1956).Google Scholar
  31. Wheeler, H. O., Cranston, W. I., Meltzer, J. I.: Hepatic uptake and biliary excretion of indocyanine green in the dog. Proc. Soc. exp. Biol. (N. T.)99, 11 (1958).Google Scholar
  32. —, Meltzer, J. I., Bradley, S. E.: Biliary transport and hepatic storage of sulfobromophthalein sodium in the unanesthetized dog, in normal man, and in patients with hepatic disease. J. clin. Invest.39, 1131 (1960).Google Scholar
  33. Whright, P. H.: Experimental insulin-deficiency due to insulin antibodies. In: E. F. Pfeiffer (Ed.): Handbuch des Diabetes mellitus, Vol. I. München: J. F. Lehmann 1969.Google Scholar
  34. Wisniewski, K., Danysz, A.: The study on the insulin controlling and directing of chlorpromazine action and level in brain tissue. Biochem. Pharmacol.15, 669 (1966).Google Scholar
  35. —, Zarebski, M.: Effect of insulin on the transport and the analgesic action of sodium salicylate. Metabolism17, 212 (1968).Google Scholar
  36. Zetterström, R., Ernster, L.: Bilirubin, an uncoupler of oxidative phosphorylation in isolated mitochondria. Nature (Lond.)178, 1335 (1956).Google Scholar

Copyright information

© Springer-Verlag 1970

Authors and Affiliations

  • B. Müller-Oerlinghausen
    • 1
    • 2
  • G. Schinke
    • 1
  1. 1.Pharmakologisches Institut der Universität GöttingenDeutschland
  2. 2.Dept. Medical SciencesMinistry of Public HealthYod-se/BangkokThailand

Personalised recommendations