Annals of Biomedical Engineering

, Volume 3, Issue 4, pp 411–432 | Cite as

Dynamic control of hepatic glucose metabolism: Studies by experiment and computer simulation

  • Richard N. Bergman
  • Mahmoud El Refai
Article
Received:

Abstract

The rates of storage and release of carbohydrate by the liver are deterined by the plasma concentrations of several bloodborne signals; most important are the concentrations of glucose, and the hormones insulin and glucagon. To understand the complex control relationships of these three signals as they affect the liver, their individual dynamic influences have been determined experimentally, and they have been integrated by means of a computer simulation of the pathways of hepatic glycogen metabolism. The simulation studies have led to specific hypotheses about the biochemical effects of glucose and insulin on the liver. The simulation studies have also led to the conclusion that glucose exerts a rapid moment-to-moment influence on the rate of uptake of glucose by the liver. Insulin, however, by exerting a slower influence on the sensitivity of the liver to glucose, is very effective in “optimizing” the amount of glucogen with the liver stores during food intake. Thus, integrated experimental and simulation studies can lead to a view of a physiological regulating system which does not emerge from either approach used alone.

Keywords

Glucose Computer Simulation Simulation Study Glucose Metabolism Glucagon 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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References

  1. Achs, M. J. Anderson, J. H., and Garfinkle, D. Gluconeogenesis in rat liver cytosol. I. Computer analysis of experimental data.Computers and Biomedical Research 1971,44, 65–106.Google Scholar
  2. Bergman, R. N., and Urquhart, J. The pilot gland approach to the study of insulin secretory dynamics.Recent Progress in Hormone Research 1971,27, 583–605.PubMedGoogle Scholar
  3. Bergman, R. N., and Bucolo, R. J. Nonlinear metabolic dynamics of the pancreas and liver.Journal of Dynamic Systems Measurement and Control 1973,95, 296–300.Google Scholar
  4. Bergman, R. N., and Azen, S. P. Measurement error inherent in the determination of hepatic glucose balance.Journal of Applied Physiology 1974,36, 269–273.PubMedGoogle Scholar
  5. Bergman, R. N., and Bucolo, R. J. Interation of insulin and glucose in the control of hepatic glucose balance.American Journal of Physiology 1974,227, 1314–1322.PubMedGoogle Scholar
  6. Bucolo, R. J., Bergman, R. N., Marsh, D. J., and Yates, F. E. Dynamics of glucose autoregulation in the isolated, blood pefused canine liver.American Journal of Physiology 1974,227, 209–217.PubMedGoogle Scholar
  7. Cerasi, E. An analog computer model for the insulin response to glucose infusion.Acta Endocrinologica 1967,55, 163–183.PubMedGoogle Scholar
  8. DeWulf, H., and Hers, H. G. The stimulation of glycogen synthesis and of glycogen synthetase in liver by the administration of glucose.European Journal of Biochemistry 1967,2, 50–56.Google Scholar
  9. El Refai, M., and Bergman, R. N. Simultion study of the control of hepatic glycogen systhesis by glucose and insulin.American Journal of Physiology (in press).Google Scholar
  10. Exton, J. H., and Park, C. R. Control of gluconeogenesis in liver. I. General features of gluconeogenesis in the perfused livers of rats.Journal of Biological Chemistry 1967,242, 2622–2636.PubMedGoogle Scholar
  11. Glismann, W. H., Hern, E. P., and Lynch, A. Intrinsic regulation of glucose output by rat liver.American Journal of Physiology 1969,216, 698–703.Google Scholar
  12. Haft, D. E. Effects of insulin on glucose metabolism by the perfused normal rat liver.American Journal of Physiology 1967,213, 219–230.Google Scholar
  13. Grodsky, G. M. A threshhold distribution hypothesis for packet storage of insulin and its mathematical modelling.Journal of Clinical Investigation 1972,51, 2047–2059.PubMedGoogle Scholar
  14. London, W. P. A thoretical study of hepatic glycogen metabolism.Journal of Biological Chemistry 1966,211, 3008–3021.Google Scholar
  15. Maddaiah, V. T., and Madsen, N. B. Kinetics of purified liver phosphorylase.Journal of Biological Chemistry 1966,241, 3873–3881.PubMedGoogle Scholar
  16. Madison, L. L. Role of insulin in the hepatic handling of glucose.Archives Internationales de Medicine Experimentale 1969,123, 284–292.Google Scholar
  17. Mersmann, H. J., and Segal, H. L. An on-off mechanism for liver glycogen synthetase activity.Proceedings of the National Academy of Sciences 1967,58, 1688–1695.Google Scholar
  18. Miller, L. L. Some direct actions of insulin, glucagon and epinephrine on the isolated, perfused rat liver.Recent Progress in Hormone Research 1961,17, 539–568.PubMedGoogle Scholar
  19. Mortimore, G. E. Effect of insulin on potassium transfer in the isolated rat liver.American Journal of Physiology 1961,200, 1315–1319.PubMedGoogle Scholar
  20. Mortimore, G. E. Influence of insulin on the hepatic uptake and release of glucose and amino acids. InHadbook of physiology, Secion 7, Vol. 1,The endocrine pancreas. Boston: Waverly, 1972. Pp. 495–504.Google Scholar
  21. Nordlie, R. C. Some properties and possibly physiological functions of phosphotrasferase activities of microsomal glucose-6-phosphatase.Annals of the New York Academy of Sciences 1966,166, 699–718.Google Scholar
  22. Ostroy, L. B. Dynamics of glucagon secretion from the isolated, blood-perfused canine pancreas. Ph.D. thesis, University of Southern California, 1974.Google Scholar
  23. Ruderman, N. B., Lauris, V., and Herrera, M. Insulin preservation of glucokinase activity in isolated, perfused rat liver.American Journal of Physiology 1967,212, 1169–1173.PubMedGoogle Scholar
  24. Shoemaker, W. C., and Elwyn, D. H. Liver: Functional interactions within the intact animal.Annual Review of Physiology 1969,31, 227–268.CrossRefPubMedGoogle Scholar
  25. Soskin, S., Essex, H. E., Herrick, J. F., and Mann, F. C. The mechanism of the regulation of the blood sugar by the liver.American Journal of Physiology 1938,124, 558–567.Google Scholar
  26. Steele, R., Bishop, J. S., Dunn, A., Altszuler, N., Rathgeb, I., and de Bodo, R. C. Inhibition of hepatic glucose production in the normal dog.American Journal of Physiology 1965,208, 301–306.PubMedGoogle Scholar
  27. Urquhart, J., and Keller, N. In situ and pilot organ perfusion techniques for the study of metabolic dynamics. InKarolinska Symposium on Research Methods in Reproductive Endocrinology, 4th Symposium, Perfusion Techniques. Stockholm: Karolinska Institute, 1971, Pp. 9–25.Google Scholar
  28. Yates, F. E., Marsh, D. J., and Iberall, A. S., Intergration of the whole organism: A Foundation for a theoretical biology. In J. A. Behnke (Ed.),Challenging biological problems: Directions toward their solution. AIBS 25-year Celebration Volume. New York: Oxford University Press, 1972. Pp. 110–132.Google Scholar

Copyright information

© Academic Press, Inc. 1975

Authors and Affiliations

  • Richard N. Bergman
    • 1
  • Mahmoud El Refai
    • 1
  1. 1.Department of Biomedical EngineeringUniversity of Southern CaliforniaLos Angeles

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