On the Mechanism of Insulin Action on Pyruvate Dehydrogenase Interconversion in Adipose Tissue

  • Otto H. Wieland
  • Ludwig Weiss
  • Georg Löffler
  • Ingrid Brunner
  • Sabine Bard


Pyruvate dehydrogenase activity of rat adipose tissue is considerably increased upon incubation with insulin due to conversion of the inactive phospho form (PDH b) to the active dephospho form (PDH a) of the enzyme. This effect depends on the presence of a metabolizable sugar such as glucose, fructose, mannose, or deoxyglucose. With pyruvate as a substrate PDH activation occurs already in the absence of insulin. Whereas nicotinate and other antilipolytic agents produced similar effects as insulin prostaglandin E1 remained ineffective under standard conditions. When adipose tissue from fasted-refed rats was taken, which is rich in glycogen, prostaglandin E1, and also insulin, led to PDH activation without the need for exogenous glucose.

Further studies carried out on isolated fat cell mitochondria pointed to the possibility that changes in mitochondrial adenine nucleotides (AN) may be involved in PDH interconversion by insulin. Increasing the ADP/ATP ratio by addition of hexokinase-glucose to mitochondrial suspensions resulted in an increase of PDH a/PDH b,whereas a decrease of ADP/ATP due to AN translocase inhibition either by atractylate or by palmityl-CoA had the opposite effect. In view of the observation that insulin lowers long chain acyl-CoA levels in adipose tissue (Denton and Halperin, 1968) its activating effect on the PDH-system may result from an increase of the mitochondrial ADP/ATP ratio due to deinhibition of AN translocase activity. The role of substrate in the mechanism of insulin action may thus in part be explained by giving rise to α-glycerophosphate which acts in lowering of long chain acyl-CoA levels due to increased re-esterification.


Adipose Tissue Insulin Stimulate Glucose Transport Pyruvate Dehydrogenase Activity Translocase Activity Insulin Adipose Tissue 
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  1. Coore, H. G., Denton, R. M., Martin, B.R., and Randle, P. J., (1971), Biochem. J., 125, 115.Google Scholar
  2. Denton, R. M., and Halperin, M. L., (1968), Biochem, J. 110, 27.Google Scholar
  3. Denton, R. M., Coore, H. G., Martin, B. R., and Randle, P. J., (1971), Nature New Biology. 231, 115.CrossRefGoogle Scholar
  4. Denton, R. M., Randle, P. J., and Martin, B. R., (1972), Biochem. J. 128, 161.Google Scholar
  5. Hepp, D., Challoner, D. R., and Williams, R. H., (1968), J. Biol. Chem., 243, 4020.Google Scholar
  6. Javorek, D., Gruber, W., and Bergmeyer, H. U., (1970), in Methoden der Enzymatischen Analyse, Bergmeyer, H. U., Ed., Weinheim, Verlag Chemie, Vol. II, p. 2051.Google Scholar
  7. Jungas, R. L., and Ball, E. G., (1964), Biochemistry, 3, 1696.Google Scholar
  8. Jungas, R. L., (1970), Endocrinology, 86, 1368.Google Scholar
  9. Jungas, R. L., and Taylor, S. I., (1972), in Insulin Action, Fritz, I.B. Ed., New York, N.Y., Academic Press, p. 269.Google Scholar
  10. Lamprecht, W., and Trautschold, I., (1970), in Methoden der Enzymatischen Analyse, Bergmeyer, H. U., Ed., Weinheim, Verlag Chemie, Vol. II, p. 2024.Google Scholar
  11. Linn, T. C., Pettit, F. H., and Reed, L. J., (1969a), Proc. Nat. Acad. Sci., U.S.A. 62, 234.Google Scholar
  12. Linn, T. C., Pettit, F. H., Hucho, F., and Reed, L. J., (1969b), Proc. Nat. Acad. Sci., U.S.A. 64, 227.Google Scholar
  13. Lopes-Cardozo, M., Vaartjes, W. J., and Van Den Bergh, S. G., (1972), Fed. Eur. Biochem. Soc. Lett., 28, 265.CrossRefGoogle Scholar
  14. Martin, B. R., and Denton, R. M., (1971), Biochem. J. 125, 105.Google Scholar
  15. Pande, S. V., and Blanchaer, M. C., (1971), J. Biol. Chem., 246, 402.Google Scholar
  16. Pettit, F. H., Roche, T. E., and Reed, L.J,, (1972), Biochem. Biophys. Res. Comm., 49, 563.CrossRefGoogle Scholar
  17. Pfaff, E., Klingenberg, M., and Heldt, H. W., (1965), Biochim. Biophys. Acta., 104, 312.CrossRefGoogle Scholar
  18. Portenhauser, R. L., and Wieland, O. H., (1972), Eur. J. Biochem., 31, 308.CrossRefGoogle Scholar
  19. Reed, L. J., Linn, T. C., Hucho, F., Namihira, G., Barrera, C. R., Roche, T. E., Pelley, J. W., and Randall, D. D., (1972), in Metabolic Interconversion of Enzymes, Wieland, O. H., Helmreich, E., Holzer, H., Eds., Berlin-HeidelbergNew York, Springer-Verlag, p. 281.CrossRefGoogle Scholar
  20. Rodbell, M., (1964), J. Biol. Chem., 239, 375.Google Scholar
  21. Sachs, L„ (1971), Statistische Auswertungsmethoden,Berlin, Heidelberg, New York, Springer-Verlag, p. 230Google Scholar
  22. Schmidt, E., (1970), in Methoden der Enzymatischen Analyse, Bergmeyer, H. U., Ed., Weinheim, Verlag Chemie, Vol. I, p. 607.Google Scholar
  23. Siess, E.A., Wittmann, J., and Wieland,O.H., (1971), Hoppe-Seyler’s Z. Physiol. Chem., 352, 447.CrossRefGoogle Scholar
  24. Siess, E. A., and Wieland, O. H., (1972), Eur. J. Biochem., 26, 96.CrossRefGoogle Scholar
  25. Taylor, S. I., Mukherjee, C., and Jungas, R. L., (1973), J. Biol. Chem., 248, 73.Google Scholar
  26. Walter, P., and Stucki, J. W., (1970), Eur. J. Biochem., 12, 508.CrossRefGoogle Scholar
  27. Weiss, L., Löffler, G., Schirmann, A., and Wieland,O.H.,(1971), Fed. Eur. Biochem. Soc. Lett., 15, 229.Google Scholar
  28. Wieland,O.H.,and v. Jagow-Westermann, B., (1969), Fed. Eur. Biochem. Soc. Lett., 3, 271.CrossRefGoogle Scholar
  29. Wieland,O.H, Siess,E.A.,and Schulze-Wethmar, F. H., (1970), First International Symposium on Metabolic Interconversion of Enzymes, S. Margherita Ligure, Abstr. p. 52.Google Scholar
  30. Wieland,O.H.,Siess,E.A.,Schulze-Wethmar, F. H., v. Funcke, H., and Winton, B., (1971), Arch. Biochem. Biophys., 143, 593.CrossRefGoogle Scholar
  31. Wieland, O. H., Patzelt, C., and Löffler, G., (1972a), Eur. J. Biochem., 26, 426.CrossRefGoogle Scholar
  32. Wieland,O.H.,Siess,E.A.,v. Funcke, H. J., Patzelt, C., Schirmann, A., Löffler, G., and Weiss, L., (1972b), in Metaboliò Interconversion of Enzymes, Wieland, O. H., Helmreich, E., and Holzer, H., Eds., Berlin, Heidelberg, New York, Springer Verlag, p. 293.CrossRefGoogle Scholar
  33. Wieland, O. H., Siess,E.A.,Weiss, L., Löffler, G., Patzelt, C., Portenhauser, R., Hartmann, U., and Schirmann, A., (1973), Society of Exp. Biol. Sympos.,27, Cambridge University Press, Cambridge, England, in press.Google Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1974

Authors and Affiliations

  • Otto H. Wieland
    • 1
  • Ludwig Weiss
    • 1
  • Georg Löffler
    • 1
  • Ingrid Brunner
    • 1
  • Sabine Bard
    • 1
  1. 1.Klinisch-chemisches Institut und Forschergruppe DiabetesStädtisches KrankenhausMünchen-SchwabingW. Germany

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