Complex bursting in pancreatic islets: a potential glycolytic mechanism

Wierschem, Keola; Bertram, Richard

doi:10.1016/j.jtbi.2004.02.022

Cited by 40 publications

(24 citation statements)

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“…However, there is also some evidence for glycolytic oscillations (Tornheim 1997). One possible role of glycolytic oscillations is in explaining the packaging of the bursts themselves into higher-order patterns, or "bursts of bursts" (Bertram and others 2004;Wierschem and Bertram 2004), and other roles are currently under investigation.…”

Section: Summary and Prospectsmentioning

confidence: 99%

Integrative modeling of the pancreatic β‐cell

Sherman¹,

Bertram²

2005

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

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Pancreatic β‐cells secrete insulin, which regulates the concentration of plasma glucose. Dysfunction of this system is a necessary contributing factor to Type II diabetes, and may be sufficient. Insulin secretion is controlled by oscillations of membrane potential, called bursting oscillations , which drive oscillations of cytosolic calcium. We describe the development of mathematical models for this mechanism, beginning with the Chay–Keizer model.

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Section: Summary and Prospectsmentioning

confidence: 99%

Integrative modeling of the pancreatic β‐cell

Sherman¹,

Bertram²

2005

Encyclopedia of Genetics, Genomics, Proteomics and Bioinformatics

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“…In the models of Sel'kov (Sel'kov 1968) and Goldbeter and Lefever (Goldbeter and Lefever 1972) ATP was considered the substrate, whose depletion provided the negative feedback as F6P does in our model, and ADP was considered the product, which provided the positive feedback, as F1,6BP does in our model. Such models can be combined with electrical activity to produce many of the patterns described here (Wierschem and Bertram 2004), but the biochemical interpretation is different. In our view, ATP acts rather as a negative modulator, which tends to shut down glycolysis when energy stores are replete, and ADP is a positive modulator, which activates glycolysis when ATP production falls behind metabolic demand.…”

Section: Metabolic Oscillationsmentioning

confidence: 99%

Electrical, Calcium, and Metabolic Oscillations in Pancreatic Islets

Bertram¹,

Sherman

Satin

2014

Islets of Langerhans

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Oscillations are an integral part of insulin secretion, and are due ultimately to oscillations in the electrical activity of pancreatic β-cells, called bursting. We discuss the underlying mechanisms for bursting oscillations in mouse islets and the parallel oscillations in intracellular calcium and metabolism. We present a unified biophysical model, called the Dual Oscillator Model, in which fast electrical oscillations are due to the feedback of Ca 2+ onto K + ion channels, and the slow component is due to oscillations in glycolysis. The combination of these mechanisms can produce the wide variety of bursting and Ca 2+oscillations observed in islets, including fast, slow, compound, and accordion bursting. We close with a description of recent experimental studies that have tested unintuitive predictions of the model and have thereby provided the best evidence to date that oscillations in glycolysis underlie the slow (~5 min) component of electrical, calcium, and metabolic oscillations in mouse islets. Keywords: bursting, insulin secretion, islet, pulsatility, oscillationsLike many neurons and endocrine cells, pancreatic β-cells are electrically excitable, producing electrical impulses in response to elevations in glucose. The electrical spiking pattern typically comes in the form of bursting, and is most well studied in mouse islets. Bursting is characterized as periodic clusters of impulses followed by silent phases when there is a cessation of impulse firing (Fig. 1). In this chapter we discuss the different types of bursting patterns observed in mouse islets and the underlying mechanisms for these oscillations and parallel oscillations in intracellular Ca 2+ and metabolism.Figure 1: Intracellular free Ca 2+ concentration measured using fura-2/AM (top) and electrical bursting (bottom) recorded from a mouse islet. Reprinted from Zhang et al. (2003).Bursting electrical activity is important since it leads to oscillations in the intracellular free Ca 2+concentration (Santos et al. 1991;Beauvois et al. 2006), which in turn lead to oscillations in insulin secretion (Gilon et al. 1993). Oscillatory insulin levels have been measured in vivo (Lang et al. 1981;Pørksen et al. 1995;Pørksen 2002;, and sampling from the hepatic portal vein in rats, dogs, and humans shows large oscillations with period of 4 to 5 min (Song et al. 2000;Matveyenko et al. 2008). Deconvolution analysis demonstrates that the oscillatory insulin level is due to oscillatory secretion of insulin from islets (Pørksen et al. 1997;Matveyenko et al. 2008), and in humans at least 75% of insulin secretion is in the form of insulin pulses (Pørksen et al. 1997). The amplitude of insulin oscillations in the peripheral blood of human subjects is ~100 times smaller than in the hepatic portal vein (Song et al. 2000). This attenuation is confirmed by findings of hepatic insulin clearance of ~50% in dogs (Polonsky et al. 1983), and ~40-80% in humans (Eaton et al. 1983;Meier et al. 2005). It has also been demonstrated that the hepatic insulin clearance ra...

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“…I K(ATP) is a back-ground hyperpolarizing current with a voltage-independent conductance, which is responsible for setting the plateau fraction, that is, the ratio of the active phase duration to the burst period. It is known that the plateau fraction increases as g K(ATP) decreases [19]. The current balance equation determining the membrane potential V is composed of the four ionic currents:…”

Section: Modelmentioning

confidence: 99%

“…Many investigations had been done in order to distinguish the role of the slow variables with different time scales in the firing patterns [18][19][20][21]. Particularly, if the slowest process of c er has no effect on the firing patterns, then it can be neglected and the model will become simpler.…”

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Dynamical analysis of bursting oscillations in the Chay-Keizer model with three time scales

Meng

Wang

2011

Sci. China Technol. Sci.

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Based on the Chay-Keizer model with three time scales, we investigate the role of the slowest variable in generating bursting oscillations in pancreatic -cells. It is shown that both of the two slow processes can interact to drive fast, medium and slow bursting oscillations typically observed in pancreatic -cells. Moreover, diverse patterns of electrical bursting are presented, including the "fold/fold" bursting, "fold/homoclinic" bursting, "fold/Hopf" bursting via "fold/fold" hysteresis loop, and the "fold/fold" bursting via point-point hysteresis loop. Fast-slow dynamics is used to analyze the types and generation mechanisms of these bursting oscillations. The results can be instructive for understanding the role of the slow variables and the current conductance in pancreatic -cells activities. Chay-Keizer model, fast-slow dynamics analysis, bifurcation Citation:Meng P, Lu Q S, Wang Q Y. Dynamical analysis of bursting oscillations in the Chay-Keizer model with three time scales.Pancreatic -cells are located in cell clusters within pancreatic islets of Langerhans and are responsible for secreting insulin in response to an elevation in the blood glucose level. This allows tissues such as muscle and fat to take up glucose as a fuel and provides the negative feedback needed to keep glucose in the normal range in the face of fluctuations of intake through the diet. Malfunctioning -cells can contribute to the development of Type II diabetes [1]. Pancreatic -cells are electrically excitable [2]. A major focus of theoretical work has been -cells dynamics, particularly in the form of bursting electrical activity [3, 4]. Bursting is a relatively slow rhythmic alternation between an active phase of rapid spiking and a quiescent phase without spiking. In fact, besides pancreatic -cells, bursting was also found in many neuron cells, including the neuron R15 [5], thalamic neurons [6], pyramidal neurons [7], trigeminal neurons [8], etc.In bursting model, the system can be separated into a "fast" subsystem and a "slow" subsystem, respectively, so there are at least two different time scales. The ''fast'' subsystem consists of the variables that change significantly only over the duration of the active phase of bursting, whereas the "slow" subsystem is represented by the variables that have a little change over the duration of the whole phase of bursting. The fast subsystem bifurcation diagram is constructed in which the ''slow'' variables are used as bifurcation parameters. And then the bursting trajectory of the full system is superimposed on the bifurcation diagram of the fast subsystem to see how the slow variables sweep back and forth through different regimes of the fast subsystem and thereby create the alternating active and silent phases of burst pattern. This is exactly the fast-slow dynamics analysis proposed by Rinzel [9]. By using the fast-slow dynamics analysis, the mechanisms of bursting oscillations in neurons

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Complex bursting in pancreatic islets: a potential glycolytic mechanism

Cited by 40 publications

References 35 publications

Integrative modeling of the pancreatic β‐cell

Integrative modeling of the pancreatic β‐cell

Electrical, Calcium, and Metabolic Oscillations in Pancreatic Islets

Dynamical analysis of bursting oscillations in the Chay-Keizer model with three time scales

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