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We propose a detailed computational beta cell model that emphasizes the role of anaplerotic metabolism under glucose and glucose-glutamine stimulation. This model goes beyond the traditional focus on mitochondrial oxidative phosphorylation and ATP-sensitive K + channels, highlighting the predominant generation of ATP from phosphoenolpyruvate in the vicinity of K ATP channels. It also underlines the modulatory role of H 2 O 2 as a signaling molecule in the first phase of glucose-stimulated insulin secretion. In the second phase, the model emphasizes the critical role of anaplerotic pathways, activated by glucose stimulation via pyruvate carboxylase and by glutamine via glutamate dehydrogenase. It particularly focuses on the production of NADPH and glutamate as key enhancers of insulin secretion. The predictions of the model are consistent with empirical data, highlighting the complex interplay of metabolic pathways and emphasizing the primary role of glucose and the facilitating role of glutamine in insulin secretion. By delineating these crucial metabolic pathways, the model provides valuable insights into potential therapeutic targets for diabetes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Calcium signaling controls several essential physiological functions in different cell types. Hence, it is not surprising that different aspects of Ca(2+) dynamics are in the focus of in-depth and extensive investigations. Efforts concentrate on the development of proper theoretical models that would provide a unified description of Ca(2+) signaling. Remarkably, experimentally recorded Ca(2+) signals exhibit a rather large diversity, which can be observed irrespective of the cell type, measuring techniques, or the nature of the signal. Our goal in the present study therefore is to present a theoretical explanation for the variability observed in experiments, whereby we focus on caffeine-induced Ca(2+) responses in isolated airway myocytes. By employing a stochastic model, we first test whether the observed variability can be attributed to intrinsic fluctuations that are a common feature of biochemical reactions that govern Ca(2+) signalization. We find that stochastic effects, within ranges that correspond to actual conditions in the cell, are far too modest to explain the large diversity observed in experimental data. Foremost, we reveal that only cell variability in theoretical modeling can appropriately describe the observed diversity in single-cell responses.

Calcium ions are an important second messenger in living cells. Calcium signals in form of waves serve as a means of intercellular communication and thus represent a vibrant subject for experimental and theoretical investigations. Here we study the role of cellular variability on the occurrence of Ca2+ wave propagation in a net of diffusively coupled cells. Dynamics of individual cells is simulated by a mathematical model for Ca2+ oscillations. Structural diversity of cells is introduced via variations of the bifurcation parameters, which signify cell sensitivity for external stimulation. Remarkably, for sufficient values of variability Ca2+ waves emerge, which are mostly ordered for intermediate variability strength. We analyze the spatial profile via the autocorrelation function, which confirms a resonance-like response due to the cellular variability. Thus, the reported phenomenon is a novel observation of diversity-induced spatial coherence resonance in a tissue-like media.

We show that in a spatially extended excitable medium, presently modelled with diffusively coupled FitzHugh-Nagumo neurons, internal stochasticity is able to extract a characteristic spatial frequency of waves on the spatial grid. Internal noise is introduced via a stochastic simulation method and is the only agent acting on the system. Remarkably, the spatial periodicity is best pronounced at an intermediate level of internal stochasticity. Thus, the reported phenomenon is an observation of internal noise spatial coherence resonance in excitable biochemical media.