1. From isles of Königsberg to islets of Langerhans: examining the function of the endocrine pancreas through network scienceAndraž Stožer, Marko Šterk, Eva Paradiž, Rene Markovič, Maša Skelin, Cara E. Ellis, Lidija Križančić Bombek, Jurij Dolenšek, Patrick E. MacDonald, Marko Gosak, 2022, review article Abstract: Islets of Langerhans are multicellular microorgans located in the pancreas that play a central role in whole-body energy homeostasis. Through secretion of insulin and other hormones they regulate postprandial storage and interprandial usage of energy-rich nutrients. In these clusters of hormone-secreting endocrine cells, intricate cell-cell communication is essential for proper function. Electrical coupling between the insulin-secreting beta cells through gap junctions composed of connexin36 is particularly important, as it provides the required, most important, basis for coordinated responses of the beta cell population. The increasing evidence that gap-junctional communication and its modulation are vital to well-regulated secretion of insulin has stimulated immense interest in how subpopulations of heterogeneous beta cells are functionally arranged throughout the islets and how they mediate intercellular signals. In the last decade, several novel techniques have been proposed to assess cooperation between cells in islets, including the prosperous combination of multicellular imaging and network science. In the present contribution, we review recent advances related to the application of complex network approaches to uncover the functional connectivity patterns among cells within the islets. We first provide an accessible introduction to the basic principles of network theory, enumerating the measures characterizing the intercellular interactions and quantifying the functional integration and segregation of a multicellular system. Then we describe methodological approaches to construct functional beta cell networks, point out possible pitfalls, and specify the functional implications of beta cell network examinations. We continue by highlighting the recent findings obtained through advanced multicellular imaging techniques supported by network-based analyses, giving special emphasis to the current developments in both mouse and human islets, as well as outlining challenges offered by the multilayer network formalism in exploring the collective activity of islet cell populations. Finally, we emphasize that the combination of these imaging techniques and network-based analyses does not only represent an innovative concept that can be used to describe and interpret the physiology of islets, but also provides fertile ground for delineating normal from pathological function and for quantifying the changes in islet communication networks associated with the development of diabetes mellitus.
Keywords: pancreatic islets, beta cells, calcium imaging, intercellular communication, functional networks, multilayer networks
Published in DKUM: 20.12.2024; Views: 0; Downloads: 76
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2. pH-dependence of glucose- dependent activity of beta cell networks in acute mouse pancreatic tissue sliceSandra Postić, Marko Gosak, Wen-Hao Tsai, Johannes Pfabe, Srdjan Sarikas, Andraž Stožer, Dean Korošak, Shi-Bing Yang, Marjan Rupnik, 2022, original scientific article Abstract: Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function. To explain this effect, a number of mechanisms was proposed involving both extracellular and intracellular targets and pathways. Here, we focus on reassessing the influence of extracellular pH on glucose-dependent beta cell activation and collective activity in physiological conditions. To this end we employed mouse pancreatic tissue slices to perform high-temporally resolved functional imaging of cytosolic Ca2+ oscillations. We investigated the effect of either physiological H+ excess or depletion on the activation properties as well as on the collective activity of beta cell in an islet. Our results indicate that lowered pH invokes activation of a subset of beta cells in substimulatory glucose concentrations, enhances the average activity of beta cells, and alters the beta cell network properties in an islet. The enhanced average activity of beta cells was determined indirectly utilizing cytosolic Ca2+ imaging, while direct measuring of insulin secretion confirmed that this enhanced activity is accompanied by a higher insulin release. Furthermore, reduced functional connectivity and higher functional segregation at lower pH, both signs of a reduced intercellular communication, do not necessary result in an impaired insulin release.
Keywords: insulin secretion, membrane excitability, potassium channels, beta cell network, collective activity, calcium waves, pancreatic islets, pH-dependence
Published in DKUM: 01.07.2024; Views: 149; Downloads: 6
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3. Collective sensing of ß-cells generates the metabolic codeDean Korošak, Marjan Rupnik, 2018, original scientific article Keywords: collective sensing, pancreatic islets, spin glass models, metabolic code, Ca2+ imaging, Ca2+ signaling, correlations, intercellular communication
Published in DKUM: 25.01.2018; Views: 1646; Downloads: 130
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4. Spatial network representation of complex living tissuesDean Korošak, Marjan Rupnik, 2008, published scientific conference contribution Abstract: Networks were widely used to describe organizational and functional principles of living organisms across various scales. The topology of such biological complex networks often turned out to be "scale-free", with the power-law distribution of number of links per node, robust and modular with underlying self-similar structure. However, the topology of cytoarchitecture in living tissues has not yet received wide attention from the network perspective. Here we discuss the spatial complex network model of coupled clusters of beta cells in pancreatic islets. Networks of cells in pancreatic islets were constructed from the 2D section images presenting fluorescently labelled intercellular spaces obtained by two-photon laser scanning microscopy of whole pancreas tissue slices, and cells conductances measured electrophysiologically using whole-cell patch-clamp. We find that the heterogeneity of beta cells in intact living islets induces scale-free topology of the tissue network. Furthermore, we show that the islet-like structures visually similar to 2D section images can be obtained using Voronoi diagrams of random points.
Keywords: pancreatic islets, betta cells, complex networks, cytoarchitecture
Published in DKUM: 31.05.2012; Views: 2255; Downloads: 81
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