Abstract
Pancreatic β-cells in intact islets of Langerhans perfused with various glucose concentrations exhibit periodic bursting electrical activity (BEA) consisting of active and silent phases. The fraction of the time spent in the active phase is called the plateau fraction and appears to be strongly correlated with the rate of release of insulin from islets as glucose concentration is varied. Here this correlation is quantified and a theoretical development is presented in detail. Experimental rates of insulin release are correlated with “effective” plateau fractions over a range of glucose concentrations. There are a number of different models for BEA in pancreatic β-cells and a method is developed here to quantify the dependence of a glucose dependent parameter on glucose concentration. As an example, the plateau fractions computed from the Sherman-Rinzel-Keizer model are matched with experimental plateau fractions to obtain a relationship between the model's glucose-dependent parameter, β, and glucose concentration. Knowledge of the relationships between β and glucose concentration and between experimental measurements of rates of insulin release and plateau fractions permits the determination of theoretical rates of insulin release from the model.
Similar content being viewed by others
Literature
Ashcroft, S. J. H., J. M. Bassett and P. J. Randle. 1972. Insulin secretion mechanisms and glucose metabolism in isolated islets.Diabetes (Suppl. 2)21, 538–545.
Ashcroft, F. and P. Rorsman. 1989. Electrophysiology of the pancreatic β-cell.Prog. Biophys. Mol. Biol. 54, 87–143.
Atwater, I., A. Goncalves, A. Herchuelz, P. Lebrun, W. J. Malaisse, E. Rojas and A. Scott. 1984. Cooling dissociates glucose-induced insulin release from electrical activity and cation fluxes in rodent pancreatic islets.J. Physiol. (Lond.) 348, 615–627.
Atwater, I., B. Ribalet and E. Rojas. 1978a. Cyclic changes in potential and resistance of the β-cell membrane induced by gluclose in islets of Langerhans from mouse.J. Physiol. (Lond.) 278, 117–139.
Atwater, I., B. Ribalet and E. Rojas. 1978b. Mouse pancreatic β-cells: tetraethylammonium blockage of the potassium permeability increase induced by depolarization.J. Physiol. (Lond.) 288, 561–574.
Atwater, I., C. M. Dawson, B. Ribalet and E. Rojas. 1978. Potassium permeability activated by intracellular calcium ion concentration in the pancreatic β-cell.J. Physiol. (Lond.) 288, 575–588.
Atwater, I., C. M. Dawson, A. Scott, G. Eddelstone and E. Rojas. 1980. The nature of the oscillatory behaviour in electrical activity from pancreatic β-cellHorm. and Metab. Res. (Suppl.)10, 100–107.
Beigelman, M., B. Ribalet and I. Atwater. 1977. Electrical activity of mouse pancreatic beta-cells: II. Effects of glucose and arginine.J. Physiol. (Paris) 73, 201–217.
Bokvist, K., P. Rorsman and P. A. Smith 1990. Block of ATP-regulated and Ca2+-activated K+ channels in mouse pancreatic β-cells by external tetraethylammonium and quinine.J. Physiol. (Lond.) 423, 327–342.
Chay, T. R. and J. Keizer. 1983. Minimal model for membrane oscillations in the pancreatic β-cell.Biophys. J. 42, 181–189.
Cook, D. L. 1984. Electrical pacemaker mechanisms of pancreatic islet cells.Federation Proc. 43, 2368–2372.
Cook, D. L., L. S. Satin and W. Hopkins. 1991. Pancreatic β-cells are bursting, but how?Trends in Neurosci. 14, 411–414.
Dean, P. M. and E. K. Matthews. 1970a. Glucose-induced electrical activity in pancreatic islet cells.J. Physiol. (Lond.) 210, 255–264.
Dean, P. M. and E. K. Matthews. 1970b. Electrical activity in pancreatic islet cells: effects of ions.J. Physiol. (Lond.) 210, 265–275.
de Vries, G., R. M. Miura and M. Pernarowski. 1994. Analysis of models of pancreatic β-cells exhibiting temporal pattern formations. InPattern Formation: Symmetry Methods and Applications, J. Chadam, M. Golubitsky, W. Langford and B. Wetton (Eds). Providence: American Mathematical Society.
Fatherazi, S. and D. L. Cook. 1991. Specificity of tetraethylammonium and quinine for three K channels in insulin-secreting cells.J. Membrane Biol. 120, 105–114.
Gembal, M., P. Gilon and J. Henquin. 1992. Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells.J. Clin. Invest. 89, 1288–1295.
Gilon, P., R. M. Shepherd and J. Henquin. 1993. Oscillations of secretion driven by oscillations of cytoplasmic Ca2+ as evidenced in single pancreatic islets.J. biol. Chem. 268, 22,265–22,268.
Henquin, J. 1990a. Glucose-induced electrical activity in β-cells, feedback control of ATP-sensitive K+ channels by Ca2+.Diabetes 39, 1457–1460.
Henquin, J. 1990b. Role of voltage- and Ca2+-dependent K+ channels in the control of glucose-induced electrical activity in pancreatic β-cells.Pflügers Arch 416, 568–572.
Henquin, J. C. and H. P. Meissner. 1984. Effects of theophylline and dibutyryl cyclic adenosine monophosphate on the membrane-potential of mouse pancreatic β-cells.J. Physiol. (Lond.) 351, 595–612.
Hodgkin, A. L. and A. F. Huxley. 1952. A quantitative description of membrane current and its application to conduction and excitation in nerve.J. Physiol. (Lond.) 117, 500–544.
Hopkins, W., L. S. Satin and D. L. Cook. 1991. Inactivation kinetics and pharmacology distinguish two calcium currents in mouse pancreatic β-cells.J. Membrane Biol. 119, 229–239.
Keizer, J. and P. Smolen. 1991. Bursting electrical activity in pancreatic β cells caused by Ca+-and voltage-inactivated Ca2+ channels.Proc. natn. Acad. Sci. U.S.A. 88, 3897–3901.
Meissner, H. P. and M. Preissler. 1979. Glucose-induced changes in the membrane potential of pancreatic B cells: their significance for the regulation of insulin release. InTreatment of Early Diabetes, R. A. Camerini-Davalos and B. Hanover (Eds), pp. 97–107. New York: Plenum.
Meissner, H. P. and M. Preissler. 1980. Ionic mechanisms of the glucose-induced membrane potential changes in β-cells.Horm. and Metab. Res. (Suppl.)10, 91–99.
Meissner, H. P. and H. Schmelz. 1974. Membrane potential of beta-cells in pancreatic islets.Pflüegers Arch. 351, 195–206.
Ozawa, S. and O. Sand. 1986. Electrophysiology of endocrine cells.Physiol. Rev. 66, 887–952.
Pernarowski, M., R. M. Miura and J. Kevorkian. 1991. The Sherman-Rinzel-Keizer model for bursting electrical activity in the pancreatic β-cell. InDifferential Equation Models in Population Dynamics and Physiology, S. Busenberg and M. Martelli (Eds), pp. 34–53. Berlin: Springer-Verlag.
Pernarowski, M., R. M. Miura and J. Kevorkian. 1992. Perturbation techniques for models of bursting electrical activity in pancreatic β-cells.SIAM J. Appl. Math. 52, 1627–1650.
Rinzel, J., T. R. Chay, D. Himmel and I. Atwater. 1986. Prediction of the glucose-induced changes in membrane ionic permeability and cytosolic Ca2+ by mathematical modelling.Adv. exp. Med. Biol. 21, 247–263.
Rorsman, P. and G. Trube, 1986. Calcium and delayed potassium currents in mouse pancreatic β-cells under voltage-clamp conditions.J. Physiol. (Lond.) 374, 531–550.
Rosario, L. M., I. Atwater and E. Rojas. 1985. Membrane potential measurements in islets of Langerhans from ob/ob obese mice suggest an alteration in [Ca]2+-activated K+ permeability.Q. J. exp. Physiol. 70, 137–150.
Santos, R. M., L. M. Rosario, A. Nadal, J. Garcia-Sancho B. Soria and B. Soria and M. Valdeolmillos., 1991. Widespread synchronous [Ca2+]i oscillations due to bursting electrical activity in single pancreatic islets.Pflügers Arch. 418, 417–422.
Satin, L. S. and D. L. Cook. 1988. Evidence for two calcium currents in insulin-secreting cells.Pflüegers Arch. 411, 401–409.
Satin, L. S. and D. L. Cook. 1989. Calcium current inactivation in insulin-secreting cells is mediated by calcium influx and membrane depolarization.Pflügers Arch. 414, 1–10.
Scott, A. M., I. Atwater and E. Rojas. 1981. A method for the simultaneous, measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans.Diabetologia 21, 470–475.
Sherman, A. and J. Rinzel. 1992. Rhythmogenic effects of weak electrotonic coupling in neuronal models.Proc. natn. Acad. Sci. U.S.A. 89, 2471–2474.
Sherman, A., J. Rinzel and J. Keizer. 1988. Emergence of organized bursting in clusters of pancreatic β-cells by channel sharing.Biophys. J. 54, 411–425.
Smolen, P. and J. Keizer. 1992. Slow voltage inactivation of Ca2+ currents and bursting mechanisms for the mouse pancreatic beta-cells.J. Membrane Biol. 127, 9–19.
Strumwasser, F. 1968. Membrane and intracellular mechanism governing endogenous, activity in neurons. InPhysiological and Biochemical Aspects of Nervous Integration, F. D. Carlson (Ed.), pp. 329–342. Englewood Cliffs: Printice-Hall.
Valdeolmillos, M., R. M. Santos, D. Contreras, B. Soria and L. M. Rosario. 1989. Glucose-induced oscillations of intracellular Ca2+ concentration resembling bursting electrical activity in single mouse islets of Langerhans.FEBS Lett. 259, 19–23.
Wollheim, C. B. and W. F. Pralong. 1990. Cytoplasmic calcium ions and other signalling events in insulin secretion.Biochem. Soc. Trans. 18, 111–114.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miura, R.M., Pernarowski, M. Correlations of rates of insulin release from islets and plateau fractions for β-cells. Bltn Mathcal Biology 57, 229–246 (1995). https://doi.org/10.1007/BF02460617
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02460617