Selection of in-phase or out-of-phase synchronization in a model based on global coupling of cells undergoing metabolic oscillations
Chaos 18, 037127 (2008); doi:10.1063/1.2983753
Published 22 September 2008
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On the basis of experimental observations, it has been suggested that glycolytic oscillations underlie the pulsatile secretion of insulin by pancreatic
cells, with a periodicity of about 13 min. If
cells within an islet are synchronized through gap junctions, the question arises as to how
cells located in different islets of Langerhans synchronize to produce oscillations in plasma levels of insulin. We address this question by means of a minimal model that incorporates the secretion of insulin by cells undergoing glycolytic oscillations. Global coupling and synchronization result from the inhibition exerted by insulin on the production of glucose, which serves as the substrate for metabolic oscillations. Glycolytic oscillations are described by a simple two-variable model centered on the product-activated reaction catalyzed by the allosteric enzyme phosphofructokinase. We obtain bifurcation diagrams for the cases in which insulin secretion is controlled solely by the product or by the substrate of the metabolic oscillator. Remarkably, we find that the oscillating cells in these conditions synchronize, respectively, in phase or out of phase. Numerical simulations show that in-phase and out-of-phase synchronization can sometimes coexist when insulin release is controlled by both the substrate and the product of the metabolic oscillator. The results provide an example of a system in which the selection of in-phase or out-of-phase synchronization is governed by the nature of the coupling between the intracellular oscillations and the secretion of the biochemical signal through which the oscillating cells are globally coupled.
©2008 American Institute of Physics
cells, with a periodicity of about 13 min. If
cells within an islet are synchronized through gap junctions, the question arises as to how
cells located in different islets of Langerhans synchronize to produce oscillations in plasma levels of insulin. We address this question by means of a minimal model that incorporates the secretion of insulin by cells undergoing glycolytic oscillations. Global coupling and synchronization result from the inhibition exerted by insulin on the production of glucose, which serves as the substrate for metabolic oscillations. Glycolytic oscillations are described by a simple two-variable model centered on the product-activated reaction catalyzed by the allosteric enzyme phosphofructokinase. We obtain bifurcation diagrams for the cases in which insulin secretion is controlled solely by the product or by the substrate of the metabolic oscillator. Remarkably, we find that the oscillating cells in these conditions synchronize, respectively, in phase or out of phase. Numerical simulations show that in-phase and out-of-phase synchronization can sometimes coexist when insulin release is controlled by both the substrate and the product of the metabolic oscillator. The results provide an example of a system in which the selection of in-phase or out-of-phase synchronization is governed by the nature of the coupling between the intracellular oscillations and the secretion of the biochemical signal through which the oscillating cells are globally coupled.
©2008 American Institute of Physics
| History: | Received 27 June 2008; accepted 28 August 2008; published 22 September 2008 |
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http://link.aip.org/link/?CHAOEH/18/037127/1 |
REFERENCES (50)
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- H. F. Chou and E. Ipp, “Pulsatile insulin secretion in isolated rat islets,”
Diabetes 39, 112 (1990) . - P. Gilon, M. A. Ravier, J. C. Jonas, and J. C. Henquin, “Control mechanisms of the oscillations of insulin secretion in vitro and in vivo,”
Diabetes 51, S144 (2002) . - N. Pørksen, M. Hollingdal, C. Juhl, P. Butler, J. D. Veldhuis, and O. Schmitz, “Pulsatile insulin secretion: Detection, regulation, and role in diabetes,”
Diabetes 51, S245 (2002) . - P. E. MacDonald and P. Rorsman, “Oscillations, intercellular coupling, and insulin secretion in pancreatic beta cells,”
PLoS Biol. 4, e49 (2006) . - R. Bertram, A. Sherman, and L. S. Satin, “Metabolic and electrical oscillations: Partners in controlling pulsatile insulin secretion,” Am. J. Physiol. 293, E890 (2007).
- D. A. Lang, D. R. Matthews, J. Peto, and R. C. Turner, “Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings,”
N. Engl. J. Med. 301, 1023 (1979) . - C. S. Mao, N. Berman, K. Roberts, and E. Ipp, “Glucose entrainment of high-frequency plasma insulin oscillations in control and type2 diabetic subjects,”
Diabetes 48, 714 (1999) . - C. S. Mao, N. Berman, and E. Ipp, “Loss of entrainment of high-frequency plasma insulin oscillations in type 2 diabetes is likely a glucose-specific beta-cell defect,” Am. J. Physiol. 287, E50 (2004).
- E. Heart and P. J. Smith, “Rhythm of the beta-cell oscillator is not governed by a single regulator: Multiple systems contribute to oscillatory behavior,” Am. J. Physiol. 292, E1295 (2007).
- H. F. Chou, N. Berman, and E. Ipp, “Oscillations of lactate release from islets of Langerhans: Evidence for oscillatory glycolysis in beta-cells,”
Am. J. Physiol. 262, E800 (1992) . - K. Tornheim, “Are metabolic oscillations responsible for normal oscillatory insulin secretion?”
Diabetes 46, 1375 (1997) . - A. K. Ghosh and B. Chance, “Oscillations of glycolytic intermediates in yeast cells,”
Biochem. Biophys. Res. Commun. 16, 174 (1964) . - B. Hess, A. Boiteux, and J. Krüger, “Cooperation of glycolytic enzymes,”
Adv. Enzyme Regul. 7, 149 (1969) . - A. Goldbeter, Biochemical Oscillations and Cellular Rhythms: The Molecular Bases of Periodic and Chaotic Behavior (Cambridge University Press, Cambridge, 1996).
- M. F. Madsen, S. Danø, and P. G. Sørensen, “On the mechanisms of glycolytic oscillations in yeast,” FEBS J. 272, 2648 (2005).
- M. A. Ravier, M. Güldenagel, A. Charollais, A. Gjinovci, D. Caille, G. Söhl, C. B. Wollheim, K. Willecke, J. C. Henquin, and P. Meda, “Loss of connexin 36 channels alters
-cell coupling, islet synchronization of glucose-induced Ca2+ and insulin oscillations, and basal insulin release,”
Diabetes 54, 1798 (2005) . - J. V. Rocheleau, M. S. Remedi, B. Granada, W. S. Head, J. C. Koster, C. G. Nichols, and D. W. Piston, “Critical role of gap junction coupled KATP channel activity for regulated insulin secretion,”
PLoS Biol. 4, e26 (2006) . - J. I. Stagner and E. Samols, “Role of intrapancreatic ganglia in regulation of periodic insular secretions,”
Am. J. Physiol. 248, E522 (1985) . - J. Sturis, E. Van Cauter, J. D. Blackman, and K. S. Polonsky, “Entrainment of pulsatile insulin secretion by oscillatory glucose infusion,”
J. Clin. Invest. 87, 439 (1991) . - A. T. Winfree, “Biological rhythms and the behavior of populations of coupled oscillators,”
J. Theor. Biol. 16, 15 (1967) . - Y. Kuramoto, Chemical Oscillations, Waves, and Turbulence (Springer, New York, 1984).
- R. E. Mirollo and S. H. Strogatz, “Synchronization of pulse-coupled biological oscillators,”
SIAM J. Appl. Math. 50, 1645 (1990) . - G. B. Ermentrout, “Stable periodic solutions to discrete and continuum arrays of weakly coupled nonlinear oscillators,”
SIAM J. Appl. Math. 52, 1665 (1992) . - A. Pikovsky, M. Rosenblum, and J. Kurths, Synchronization: A Universal Concept in Nonlinear Science (Cambridge University Press, Cambridge, 2001).
- N. Kopell, G. B. Ermentrout, M. A. Whittington, and R. D. Traub, “Gamma rhythms and beta rhythms have different synchronization properties,”
Proc. Natl. Acad. Sci. U.S.A. 97, 1867 (2000) . - T. J. Lewis and J. Rinzel, “Dynamics of spiking neurons connected by both inhibitory and electrical coupling,”
J. Comput. Neurosci. 14, 283 (2003) . - E. M. Izhikevich, Dynamical Systems in Neuroscience: The Geometry of Excitability and Bursting (MIT Press, Cambridge, MA, 2007).
- A. Sherman, J. Rinzel, and J. Keizer, “Emergence of organized bursting in clusters of pancreatic b-cells by channel sharing,”
Biophys. J. 54, 411 (1988) . - C. L. Stokes and J. Rinzel, “Diffusion of extracellular K+ can synchronize bursting oscillations in a model islet of Langerhans,”
Biophys. J. 65, 597 (1993) . - M. G. Pedersen, R. Bertram, and A. Sherman, “Intra- and inter-islet synchronization of metabolically driven insulin secretion,”
Biophys. J. 89, 107 (2005) . - Y. X. Li, J. Halloy, J. L. Martiel, and A. Goldbeter, “Suppression of chaos and other dynamical transitions induced by intercellular coupling in a model for cyclic AMP signaling in Dictyostelium cells,” Chaos 2, 501 (1992).
- S. De Monte, F. d'Ovidio, S. Danø, and P. G. Sørensen, “Dynamical quorum sensing: Population density encoded in cellular dynamics,”
Proc. Natl. Acad. Sci. U.S.A. 104, 18377 (2007) . - J. Wolf and R. Heinrich, “Dynamics of two-component biochemical systems in interacting cells; synchronization and desynchronization of oscillations and multiple steady states,”
BioSystems 43, 1 (1997) . - J. Wolf, J. Passarge, O. J. Somsen, J. L. Snoep, R. Heinrich, and H. V. Westerhoff, “Transduction of intracellular and intercellular dynamics in yeast glycolytic oscillations,”
Biophys. J. 78, 1145 (2000) . - A. Khadra and Y. X. Li, “A model for the pulsatile secretion of gonadotropin-releasing hormone from synchronized hypothalamic neurons,”
Biophys. J. 91, 74 (2006) . - C. Liu, D. R. Weaver, S. H. Strogatz, and S. M. Reppert, “Cellular construction of a circadian clock: Period determination in the suprachiasmatic nuclei,”
Cell 91, 855 (1997) . - D. Gonze, S. Bernard, C. Waltermann, A. Kramer, and H. Herzel, “Spontaneous synchronization of coupled circadian oscillators,”
Biophys. J. 89, 120 (2005) . - T. L. To, M. A. Henson, E. D. Herzog, and F. J. Doyle III, “A molecular model for intercellular synchronization in the mammalian circadian clock,”
Biophys. J. 92, 3792 (2007) . - J. Garcia-Ojalvo, M. B. Elowitz, and S. H. Strogatz, “Modeling a synthetic multicellular clock: Repressilators coupled by quorum sensing,”
Proc. Natl. Acad. Sci. U.S.A. 101, 10955 (2004) . - K. Wierschem and R. Bertram, “Complex bursting in pancreatic islets: A potential glycolytic mechanism,”
J. Theor. Biol. 228, 513 (2004) . - R. Bertram, L. Satin, M. Zhang, P. Smolen, and A. Sherman, “Calcium and glycolysis mediate multiple bursting modes in pancreatic islets,”
Biophys. J. 87, 3074 (2004) . - C. S. Nunemaker, R. Bertram, A. Sherman, K. Tsaneva-Atanasova, C. R. Daniel, and L. S. Satin, “Glucose modulates [Ca++]i oscillations in pancreatic islets via ionic and glycolytic mechanisms,”
Biophys. J. 91, 2082 (2006) . - R. Bertram, L. S. Satin, M. G. Pedersen, D. S. Luciani, and A. Sherman, “Interaction of glycolysis and mitochondrial respiration in metabolic oscillations of pancreatic islets,”
Biophys. J. 92, 1544 (2007) . - A. Goldbeter and R. Lefever, “Dissipative structures for an allosteric model: Application to glycolytic oscillations,”
Biophys. J. 12, 1302 (1972) . - A. Goldbeter and G. Nicolis, “An allosteric enzyme model with positive feedback applied to glycolytic oscillations,” in Progress in Theoretical Biology, edited by F. Snell and R. Rosen (Academic, New York, 1976), Vol. 4, pp. 65–160.
- S. Kar and D. S. Ray, “Sustained simultaneous glycolytic and insulin oscillations in
-cells,”
J. Theor. Biol. 237, 58 (2005) . - J. Girard, “The inhibitory effects of insulin on hepatic glucose production are both direct and indirect,”
Diabetes 55, S65 (2006) . - E. B. Merriam, T. I. Netoff, and M. I. Banks, “Bistable network behavior of layer I interneurons in auditory cortex,”
J. Neurosci. 25, 6175 (2005) . - G. Houart, G. Dupont, and A. Goldbeter, “Bursting, chaos and birhythmicity originating from self-modulation of the inositol1,4,5-trisphosphate signal in a model for intracellular Ca2+ oscillations,”
Bull. Math. Biol. 61, 507 (1999) . - E. J. Doedel, “AUTO: A program for the automatic bifurcation analysis of autonomous systems,” Congr. Numer. 30, 265 (1981).







