Mathematical models of electrical activity of the pancreatic β-cell: A physiological review

Félix‐Martínez, Gerardo J.; Godínez‐Fernández, J. Rafael

doi:10.4161/19382014.2014.949195

Cited by 54 publications

(48 citation statements)

References 143 publications

(221 reference statements)

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“…These factors may be associated with impaired extracellular calcium uptake and impaired intracellular calcium release from ER (http://www.kegg.jp/kegg-bin/highlight_pathway?scale=1.0& map=map04911&keyword=insulin secretion). Impaired extracellular calcium uptake and impaired intracellular calcium release from the ER may contribute to impaired insulin and pancreatic secretion (12,13). PLC and CREB were associated with the promotion of insulin secretion and synthesis (14,15).…”

Section: A B Mir-26a-5p Mir-26b-5p Mir-27a-3p and Mir-148b-3pmentioning

confidence: 99%

Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

Tian

Ouyang

et al. 2015

Biomedical Reports

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Abstract. Network cross-talks between microRNAs (miRNAs) and mRNAs may be useful to elucidate the pathological mechanisms of pancreatic islet cells in diabetic individuals. The aim of the present study was to investigate the cross-talks between miRNAs and mRNAs in pancreatic tissues of streptozotocin-induced diabetic mice through microarray and bioinformatic methods. Based on the miRNA microarray, 64 upregulated and 72 downregulated miRNAs were observed in pancreatic tissues in diabetic mice compared to the normal controls. Based on the mRNA microarrray, 507 upregulated mRNAs and 570 downregulated mRNAs were identified in pancreatic tissues in diabetic mice compared to the normal controls. Notably, there were 246 binding points between upregulated miRNA and downregulated mRNAs; simultaneously, there were 583 binding points between downregulated miRNA and upregulated mRNAs. These changed mRNA may potentially involve the following signaling pathways: Insulin secretion, pancreatic secretion, mammalian target of rapamycin signaling pathway, forkhead box O signaling pathway and phosphatidylinositol 3-kinase-protein kinase B signaling. The fluctuating effects of miRNAs and matched mRNAs indicated that miRNAs may have wide cross-talks with mRNAs in pancreatic tissues of type 1 diabetic mice. The cross-talks may play important roles in contributing to impaired islet functions and the development of diabetes. However, further functional validation should be conducted in the future. IntroductionDiabetes mellitus is a complex metabolic disease demonstrating impaired islet function (1,2). Destruction of β-cells or the failure of these insulin-secreting cells to compensate for increased metabolic demand may account for the development of diabetes. Apoptosis, oxidative stress, mitochondrial dysfunction and endoplasmic reticulum (ER) stress responses, including c-Jun N-terminal kinase (JNK) activation, have been suggested as mechanisms for the changes of pancreatic β-cells in type 2 diabetes mellitus (T2DM) (3). T1DM is the result of autoimmune destruction of pancreatic β cells (4). However, the mechanisms involved in islet dysfunction remain unclear. microRNAs (miRNAs) play a key role in regulating islet function (5). Repression of mRNAs by miRNAs is an important mechanism for regulation of expression during cell fate specification, apoptosis and metabolism (6). In the previous study, miRNA-mRNA interactions were investigated in the pancreatic islets of spontaneously diabetic Goto-Kakizaki rats (7) and the human pluripotent stem cells based in vitro model of pancreatic differentiation (8). A number of key pairs of miRNA-mRNA were proposed to have significant roles in the pathogenesis of T2DM or islet development. However, few studies have reported the miRNA-mRNA cross-talk in T1DM.In the present study, the cross-talks between miRNAs and mRNAs in the streptozotocin (STZ)-induced T1DM mice were investigated. Materials and methodsEstablishment of T1DM mouse model. Male National Institutes of Health (NIH) mice (age, 4 weeks) were...

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Section: A B Mir-26a-5p Mir-26b-5p Mir-27a-3p and Mir-148b-3pmentioning

confidence: 99%

Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

Tian

Ouyang

et al. 2015

Biomedical Reports

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“…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

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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.

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“…The aforementioned first two steps in the transduction pathway, i.e., the change in the MP and the change in [Ca 2+ ] c , both occur in the form of oscillations that are tightly coupled within a beta cell [4,7]. In addition to the activity of voltage-dependent calcium channels, the shape of both MP and [Ca 2+ ] c oscillations seems to be determined also by the uptake and release of Ca 2+ by internal stores as well as by the flux of Ca 2+ across the plasma membrane mediated by voltage-independent calcium channels, exchangers and pumps [6,8,9]. The exact quantitative contribution of these processes in shaping [Ca 2+ ] c oscillations under stimulation with glucose or other hormonal and neuronal secretagogues in beta cells of various species and different experimental models is a matter of ongoing investigations [6].…”

Section: Introductionmentioning

confidence: 99%

Multilayer network representation of membrane potential and cytosolic calcium concentration dynamics in beta cells

Gosak

Dolenšek

Markovič

et al. 2015

Chaos, Solitons & Fractals

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a r t i c l e i n f o a b s t r a c tModern theory of networks has been recognized as a very successful methodological concept for the description and analysis of complex systems. However, some complex systems are more complex than others. For instance, several real-life systems are constituted by interdependent subsystems and their elements are subjected to different types of interactions that can also change with time. Recently, the multilayer network formalism has been proposed as a general theoretical framework for the description and analysis of such multi-dimensional complex systems and is acquiring more and more prominence in terms of a new research direction. In the present study, we use this methodology for the description of functional connectivity patterns and signal propagation between pancreatic beta cells in an islet of Langerhans at the levels of membrane potential (MP) and cytosolic calcium concentration ([Ca 2+ ] c ) dynamics to study the extent of overlap in the two networks and to clarify whether time lags between the two signals in individual cells are in any way dependent on the role these cells play in the functional networks. The two corresponding network layers are constructed on the basis of signal directions and pairwise correlations, whereas the interlayer connections represent the time lag between both measured signals. Our results confirm our previous finding that both MP and [Ca 2+ ] c change spread across an islet in the form of a depolarization and a [Ca 2+ ] c wave, respectively. Both types of waves follow nearly the same path and the networks in both layers have a similar but not entirely the same structure. We show that the observed discrepancies are attributed to variability in delays between the depolarization and rise in [Ca 2+ ] c . In particular, high-degree nodes in both layers are found to exhibit a larger time lag between the MP and the [Ca 2+ ] c signal than nodes with less connections. We speculate that this finding reflects a higher activity of endoplasmic reticulum calcium pumps in the most connected cells. Our findings indicate that visualizing and studying the temporal information flow and interaction patterns between beta cells as a multiplex network can provide valuable new insights into the physiology of the complex signaling processes in islets of Langerhans.

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Mathematical models of electrical activity of the pancreatic β-cell: A physiological review

Cited by 54 publications

References 143 publications

Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

Cross-talks between microRNAs and mRNAs in pancreatic tissues of streptozotocin-induced type 1 diabetic mice

The Pancreatic β-Cell: A Bioenergetic Perspective

Multilayer network representation of membrane potential and cytosolic calcium concentration dynamics in beta cells

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