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Annals of Biomedical Engineering

, Volume 8, Issue 4–6, pp 539–557 | Cite as

Hypercomplex models of insulin and glucose dynamics: Do they predict experimental results?

  • A. M. Albisser
  • Y. Yamasaki
  • H. Broekhuyse
  • J. Tiran
Diabetes and Endocrine Control

Abstract

A hypercomplex circulation and organs model of glucose and insulin dynamics is presented. The model is based on physiological parameters, incorporating blood and plasma flow rates, circulatory paths, intra- and extravascular glucose and insulin spaces, as well as the specific organs and tissues involved both with insulin disappearance and with glucose production or uptake. Its simulations readily lend themselves to physiological interpretation. To explore its validity, the model was assigned parameters typical of a 12 kg dog and was arranged to accept known glucose and insulin infusions from two different experiments on pancreatectomized diabetic animals. It predicted the observed glucose and insulin concentrations as well as uptake rates for both moieties in the individual organs and tissues. This confirmed the ability of the model to predict with consistency the group mean outcomes of both experiments when differing routes (portal or peripheral) of infusion were applied. Excellent agreement was achieved for the studies. The model isolates glucose uptake in the periphery, the liver, the brain, and the gut and allows a direct comparison of glucose disposal along various routes. Thus, the total amount of glucose uptake by peripheral, insulin-dependent tissues is directly calculated to be 30% of an intravenous glucose load, with peripheral infusion, which is higher than that with portal infusion (18%).

Keywords

Glucose Uptake Plasma Flow Glucose Production Diabetic Animal Insulin Infusion 
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. 1.
    Albisser, A.M., C.K. Botz, and B.S. Leibel. Blood glucose regulation using an open-loop insulin delivery system in pancreatectomized dogs given glucose infusion. I. Portal squarewaves.Diabetologia 16:129–133, 1979.CrossRefPubMedGoogle Scholar
  2. 2.
    Albisser, A.M., J. Ellman, A. Hanna, Y. Goriya, and H. Minuk. Continuous blood glucose analysis in vitro and vivo.Diabetologia 15:303, 1978.PubMedGoogle Scholar
  3. 3.
    Albisser, A.M., B.S. Leibel, T.G. Ewart, Z. Davidovac, C.K. Botz, and W. Zingg. An artificial endocrine pancreas.Diabetes 23:389–396, 1974.PubMedGoogle Scholar
  4. 4.
    Albisser, A.M., B.S. Leibel, W. Johnson, A. Denoga, C.K. Botz, and E.B. Marliss. An improved technique for the rapid continuous measurement of whole blood glucose, suitable for clinical application in an artificial endocrine pancreas.Med. Prog. Technol. 5:141–148, 1977.PubMedGoogle Scholar
  5. 5.
    Albisser, A.M., B.S. Leibel, B. Zinman, F.T. Murray, W. Zingg, C.K. Botz, A. Denoga, and E.B. Marliss. Studies with an artificial endocrine pancreas.Arch. Intern. Med. 137: 639–649, 1977.CrossRefPubMedGoogle Scholar
  6. 6.
    Albisser, A.M., B.S. Leibel, T.G. Ewart, Z. Davidovac, C.K. Botz, W. Zingg, H. Schipper, and R. Gander. Clinical control of diabetes by the artificial pancreas.Diabetes 23:397–404, 1974.PubMedGoogle Scholar
  7. 7.
    Bergman, R.N., and M. El-Refai. Dynamic control of hepatic metabolism: Studies by experimental and computer simulation.Ann. Biomed. Eng. 3:411–432, 1975.PubMedGoogle Scholar
  8. 8.
    Bergman, R.N., Y.Z. Ider, C.R. Bowden, and C. Cobelli. Quantitative estimation of insulin sensitivity.Am. J. Physiol. 236:E667-E677, 1979.PubMedGoogle Scholar
  9. 9.
    Botz, C.K., E.B. Marliss, and A.M. Albisser. Blood glucose regulation using closed- and open-loop insulin delivery system. II. Peripheral primed squarewave infusions.Diabetologia 16:45–49, 1979.Google Scholar
  10. 10.
    Cahill, G.F., and O.E. Owen. Some observations on carbohydrate metabolism in man.Carbohydrate Metabolism and its Disorders New York: Academic Press, 1968, vol. 2, pp. 502–503.Google Scholar
  11. 11.
    Cahill, G.F., and J.S. Soeldner. Glucose homeostasis: A brief review.Hormonal Control Systems, Supplement 1, Mathematical Biosciences. New York: American Elsevier, 1969.Google Scholar
  12. 12.
    Camu, F. Hepatic balances of glucose and insulin in response to physiological increments of endogenous insulin during glucose infusion in dogs.Eur. J. Clin. Invest. 5:101–108, 1975.PubMedGoogle Scholar
  13. 13.
    Cherrington, A.D., J.L. Chiasson, J.E. Liljenquist, A.S. Jennings, U. Keller, and W.W. Lacy. The role of insulin and glucagon in the regulation of basal glucose production in the postabsorptive dog.J. Clin. Invest. 58:1407–1418, 1976.PubMedGoogle Scholar
  14. 14.
    Christensen, N.J., and H. Orskov. The relationship between endogenous serum insulin concentration and glucose uptake in the forearm muscles of nondiabetics.J. Clin. Invest. 47:1262–1268, 1968.PubMedGoogle Scholar
  15. 15.
    El-Refai, M. and R.N. Bergman. Glucagon-simulated glycogenolysis: Time-dependent sensitivity to insulin.Am. J. Physiol. 236:E246-E254, 1979.PubMedGoogle Scholar
  16. 16.
    Felig, P., and J. Wahren. Fuel homeostasis in exercise.N. Engl. J. Med. 293:1078–1084, 1975.PubMedGoogle Scholar
  17. 17.
    Felig, P., J. Wahren, and R. Hendler. Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man.Diabetes 24:468–475, 1975.PubMedGoogle Scholar
  18. 18.
    Goriya, Y., A. Bahoric, E.B. Marliss, B. Zinman, and A.M. Albisser. Glycemic regulation using a programmed insulin delivery device. III. Long-term studies on diabetic dogs.Diabetes 28:558–564, 1979.PubMedGoogle Scholar
  19. 19.
    Guyton, J.R., R.C. Foster, J.S. Soeldner, M.H. Tan, C.B. Kahn, L. Kincz, and R.E. Gleason. A model of glucose insulin homeostasis in man that incorporates the heterogeneous fast pool theory of pancreatic insulin release.Diabetes 27:1027–1042, 1978.PubMedGoogle Scholar
  20. 20.
    Haerer, A.F. Pyruvate, citrate, alphaketoglutarate, and glucose in the CSF and blood of neurologic patients.Acta Neurol. Scand. 48:306–312, 1972.PubMedGoogle Scholar
  21. 21.
    Honey, R.N., and S. Price. The determination of insulin extraction in the isolated perfused rat liver.Horm. Metab. Res. 11:111–117, 1979.PubMedGoogle Scholar
  22. 22.
    Kalant, N., T. Leibovici, I. Rohan, and K. McNeill. Effect of exercise on glucose and insulin utilisation in the forearm.Metabolism 27:333–340, 1978.CrossRefPubMedGoogle Scholar
  23. 23.
    Mortimore, G.E. Influence of insulin on the hepatic uptake and release of glucose and amino acids.Handbook of Physiology, Section 7: Endocrinology Washington, D.C.: American Physiological Society, 1972, vol. 1, pp. 495–504.Google Scholar
  24. 24.
    Pitts, R.F.Physiology of Kidney and Body Fluids, 3rd Edition. Chicago: Yearbook Medical Publishers, 1974.Google Scholar
  25. 25.
    Pryce, J.D., P.W. Gant, and K.L. Saul. Normal concentrations of lactate, glucose and protein in the cerebrospinal fluid, and the diagnostic implications of abnormal concentrations.Clin. Chem. 16:562–565, 1970.PubMedGoogle Scholar
  26. 26.
    Rasio, E., M.J. Whichelow, W.J.H. Butterfield, and B.H. Hicks. Insulin fixation and glucose uptake by forearm tissues in response to infusions of physiological amounts of insulin in nondiabetic subjects.Diabetologia 8:244–249, 1972.CrossRefPubMedGoogle Scholar
  27. 27.
    Robinson, J.R. Principles of renal physiology.Renal Disease. Oxford: Blackwell, 1967, p. 67.Google Scholar
  28. 28.
    Sacca, L., R. Sherwin, and P. Felig. Effect of sequential infusions of glucagon and epinephrine on glucose turnover in the dog.Am. J. Physiol. 235:E287-E290, 1978.PubMedGoogle Scholar
  29. 29.
    Tiran, J., L.I. Avruch and A.M. Albisser. A circulation and organs model for insulin dynamics.Am. J. Physiol. 237:E331-E339, 1979.PubMedGoogle Scholar
  30. 30.
    Tiran, J., K.R. Galle, and D. Porte Jr. A simulation model of extracellular glucose distribution in the human body.Ann. Biomed. Eng. 3:34–46, 1975.PubMedGoogle Scholar
  31. 31.
    Wahren, J., P. Felig, E. Cerasi, and R. Luft. Splanchnic and peripheral glucose and amino acid metabolism in diabetes mellitus.J. Clin. Invest. 51:1870–1878, 1972.PubMedGoogle Scholar
  32. 32.
    Widdas, W.F. Membrane transport of sugar.Carbohydrate Metabolism and Its Disorders. New York: Academic Press, 1968, vol. 1, pp. 4–12.Google Scholar
  33. 33.
    Wilbrandt, W. Die permeabilitat der voten blukorperchen fur imfache sucker.Pflug. Arch. ges. Physiol. 241:302–309, 1938.Google Scholar

Copyright information

© Pergamon Press Ltd. 1981

Authors and Affiliations

  • A. M. Albisser
    • 1
  • Y. Yamasaki
    • 1
  • H. Broekhuyse
    • 2
  • J. Tiran
    • 3
  1. 1.Biomedical Research, The Hospital for Sick ChildrenTorontoCanada
  2. 2.The University of TorontoTorontoCanada
  3. 3.Ben Gurion UniversityBeer ShevaIsrael

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