Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?

Watts, Margaret; Fendler, Bernard J.; Merrins, Matthew J.; Satin, Leslie S.; Bertram, Richard; Sherman, Arthur

doi:10.1137/130920198

Cited by 21 publications

(29 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A comprehensive and critical nonmathematical overview of the multiple experi-mental and theoretical models that have been advanced to interpret the complex pattern of ␤-cell firing (e.g., Refs. 44,45,121,159,293,391,534) has recently been published (151). The most comprehensive current mathematical construction, the Dual Oscillator Model, proposes interactions between three modules: glycolysis, the mitochondrion, and the plasma membrane (46,349,534).…”

Section: Model Buildingmentioning

confidence: 99%

The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

View full text Add to dashboard Cite

The pancreatic ␤-cell secretes insulin in response to elevated plasma glucose. This review applies an external bioenergetic critique to the central processes of glucose-stimulated insulin secretion, including glycolytic and mitochondrial metabolism, the cytosolic adenine nucleotide pool, and its interaction with plasma membrane ion channels. The control mechanisms responsible for the unique responsiveness of the cell to glucose availability are discussed from bioenergetic and metabolic control standpoints. The concept of coupling factor facilitation of secretion is critiqued, and an attempt is made to unravel the bioenergetic basis of the oscillatory mechanisms controlling secretion. The need to consider the physiological constraints operating in the intact cell is emphasized throughout. The aim is to provide a coherent pathway through an extensive, complex, and sometimes bewildering literature, particularly for those unfamiliar with the field.

show abstract

Section: Model Buildingmentioning

confidence: 99%

The Pancreatic β-Cell: A Bioenergetic Perspective

Nicholls

2016

Physiological Reviews

123

View full text Add to dashboard Cite

show abstract

“…The calcium-dependent component of hydrolysis is given by k hyd , and J hyd,SS is the basal level of hydrolysis. Thus, it can be seen from (6b) that Ca c influences the rate of glycolysis [17].…”

Section: Dual Oscillator Modelmentioning

confidence: 99%

“…The range of CaD is 0.00 ď J GK ď 0.01 and J GK ě 0.176. The range of CaI is 0.045 ď J GK ď 0.15, and these parameter values are used for the β-cells [17]. Ca 2`l inks the electrical and metabolic oscillations that are exhibited by β-cells in response to elevated glucose levels in the bloodstream.…”

Section: Physiologymentioning

confidence: 99%

“…The Dual Oscillator Model (DOM) [17] represents the process of insulin secretion for a single β-cell by seven differential equations (1a)-(1g) consisting of three components: electrical, mitochondrial, and glycolytic. The DOM is given by…”

Section: Dual Oscillator Modelmentioning

confidence: 99%

“…The DOM has already been used to address questions about situations under which metabolic oscillations occur, especially focusing on the effect of calcium oscillations as newer versions of the model suggest that calcium plays a bigger role in metabolic oscillations, where certain modes require the presence of calcium oscillations for metabolic oscillations to occur. The model in Watts et al [17] has been adapted to work as a multi-cell islet model as in Eskandar et al [6]. We will consider how dynamics change when working with islet oscillations dependent on calcium oscillations.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Interaction of Calcium and Metabolic Oscillations in Pancreatic Beta-cells

Aronne¹,

Clapp²,

Jung³

et al. 2017

SPORA

Self Cite

View full text Add to dashboard Cite

Diabetes is a disease characterized by an excessive level of glucose in the bloodstream, which may be a result of improper insulin secretion. Insulin is secreted in a bursting behavior of pancreatic β-cells in islets, which is affected by oscillations of cytosolic calcium concentration. We used the Dual Oscillator Model to explore the role of calcium in calcium oscillation independent and calcium oscillation dependent modes and the synchronization of metabolic oscillations in electrically coupled β-cells. We implemented a synchronization index in order to better measure the synchronization of the β-cells within an islet, and we studied heterogeneous modes of coupled β-cells. We saw that increasing calcium coupling or voltage coupling in heterogeneous cases increases synchronization; however, in certain cases increasing both voltage and calcium coupling causes desynchronization. To better represent an islet, we altered previous code to allow for a greater number of cells to be simulated.

show abstract

Electrical, Calcium, and Metabolic Oscillations in Pancreatic Islets

Bertram¹,

Sherman

Satin

2014

Islets of Langerhans

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Calcium and Metabolic Oscillations in Pancreatic Islets: Who's Driving the Bus?

Cited by 21 publications

References 62 publications

The Pancreatic β-Cell: A Bioenergetic Perspective

The Pancreatic β-Cell: A Bioenergetic Perspective

The Interaction of Calcium and Metabolic Oscillations in Pancreatic Beta-cells

Electrical, Calcium, and Metabolic Oscillations in Pancreatic Islets

Contact Info

Product

Resources

About