The role of anaplerotic metabolism of glucose and glutamine in insulin secretion: A model approach.

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 channels. It also underlines the modulatory role of HO as a signaling molecule in the first phase of glucose-stimulated insulin secretion.

Network representation of multicellular activity in pancreatic islets: Technical considerations for functional connectivity analysis.

Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect of metabolic homeostasis. Despite the inherent heterogeneity and multimodal activity of individual cells, intercellular coupling acts as a homogenizing force, enabling coordinated responses through the propagation of intercellular waves. Disruptions in this coordination are implicated in irregular insulin secretion, a hallmark of diabetes.

Exendin-4 affects calcium signalling predominantly during activation and activity of beta cell networks in acute mouse pancreas tissue slices.

Tight control of beta cell stimulus-secretion coupling is crucial for maintaining homeostasis of energy-rich nutrients. While glucose serves as a primary regulator of this process, incretins augment beta cell function, partly by enhancing cytosolic [Ca] dynamics. However, the details of how precisely they affect beta cell recruitment during activation, their active time, and functional connectivity during plateau activity, and how they influence beta cell deactivation remain to be described.

Both electrical and metabolic coupling shape the collective multimodal activity and functional connectivity patterns in beta cell collectives: A computational model perspective.

Pancreatic beta cells are coupled excitable oscillators that synchronize their activity via different communication pathways. Their oscillatory activity manifests itself on multiple timescales and consists of bursting electrical activity, subsequent oscillations in the intracellular Ca^{2+}, as well as oscillations in metabolism and exocytosis. The coordination of the intricate activity on the multicellular level plays a key role in the regulation of physiological pulsatile insulin secretion and is incompletely understood.

The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.

Beta cells couple stimulation by glucose with insulin secretion and impairments in this coupling play a central role in diabetes mellitus. Cyclic adenosine monophosphate (cAMP) amplifies stimulus-secretion coupling via protein kinase A and guanine nucleotide exchange protein 2 (Epac2A). With the present research, we aimed to clarify the influence of cAMP-elevating diterpene forskolin on cytoplasmic calcium dynamics and intercellular network activity, which are two of the crucial elements of normal beta cell stimulus-secretion coupling, and the role of Epac2A under normal and stimulated conditions.

Determinants of collective failure in excitable networks.

We study collective failures in biologically realistic networks that consist of coupled excitable units. The networks have broad-scale degree distribution, high modularity, and small-world properties, while the excitable dynamics is determined by the paradigmatic FitzHugh-Nagumo model. We consider different coupling strengths, bifurcation distances, and various aging scenarios as potential culprits of collective failure.

Functional characteristics of hub and wave-initiator cells in β cell networks.

Islets of Langerhans operate as multicellular networks in which several hundred β cells work in synchrony to produce secretory pulses of insulin, a hormone crucial for controlling metabolic homeostasis. Their collective rhythmic activity is facilitated by gap junctional coupling and affected by their functional heterogeneity, but the details of this robust and coordinated behavior are still not fully understood. Recent advances in multicellular imaging and optogenetic and photopharmacological strategies, as well as in network science, have led to the discovery of specialized β cell subpopulations that were suggested to critically determine the collective dynamics in the islets.

Ca2+ Oscillations, Waves, and Networks in Islets From Human Donors With and Without Type 2 Diabetes.

Pancreatic islets are highly interconnected structures that produce pulses of insulin and other hormones, maintaining normal homeostasis of glucose and other nutrients. Normal stimulus-secretion and intercellular coupling are essential to regulated secretory responses, and these hallmarks are known to be altered in diabetes. In the current study, we used calcium imaging of isolated human islets to assess their collective behavior.

pH-Dependence of Glucose-Dependent Activity of Beta Cell Networks in Acute Mouse Pancreatic Tissue Slice.

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.

From Isles of Königsberg to Islets of Langerhans: Examining the Function of the Endocrine Pancreas Through Network Science.

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.

Computational modeling of targeted temperature management in post-cardiac arrest patients.

Our core body temperature is held around [Formula: see text]C by an effective internal thermoregulatory system. However, various clinical scenarios have a more favorable outcome under external temperature regulation. Therapeutic hypothermia, for example, was found beneficial for the outcome of resuscitated cardiac arrest patients due to its protection against cerebral ischemia.

Calcium imaging in intact mouse acinar cells in acute pancreas tissue slices.

The physiology and pathophysiology of the exocrine pancreas are in close connection to changes in intra-cellular Ca2+ concentration. Most of our knowledge is based on in vitro experiments on acinar cells or acini enzymatically isolated from their surroundings, which can alter their structure, physiology, and limit our understanding. Due to these limitations, the acute pancreas tissue slice technique was introduced almost two decades ago as a complementary approach to assess the morphology and physiology of both the endocrine and exocrine pancreas in a more conserved in situ setting.

Interlayer Connectivity Affects the Coherence Resonance and Population Activity Patterns in Two-Layered Networks of Excitatory and Inhibitory Neurons.

The firing patterns of neuronal populations often exhibit emergent collective oscillations, which can display substantial regularity even though the dynamics of individual elements is very stochastic. One of the many phenomena that is often studied in this context is coherence resonance, where additional noise leads to improved regularity of spiking activity in neurons. In this work, we investigate how the coherence resonance phenomenon manifests itself in populations of excitatory and inhibitory neurons.

Networks behind the morphology and structural design of living systems.

Technological advances in imaging techniques and biometric data acquisition have enabled us to apply methods of network science to study the morphology and structural design of organelles, organs, and tissues, as well as the coordinated interactions among them that yield a healthy physiology at the level of whole organisms. We here review research dedicated to these advances, in particular focusing on networks between cells, the topology of multicellular structures, neural interactions, fluid transportation networks, and anatomical networks. The percolation of blood vessels, structural connectivity within the brain, the porous structure of bones, and relations between different anatomical parts of the human body are just some of the examples that we explore in detail.

The Role of cAMP in Beta Cell Stimulus-Secretion and Intercellular Coupling.

Pancreatic beta cells secrete insulin in response to stimulation with glucose and other nutrients, and impaired insulin secretion plays a central role in development of diabetes mellitus. Pharmacological management of diabetes includes various antidiabetic drugs, including incretins. The incretin hormones, glucagon-like peptide-1 and gastric inhibitory polypeptide, potentiate glucose-stimulated insulin secretion by binding to G protein-coupled receptors, resulting in stimulation of adenylate cyclase and production of the secondary messenger cAMP, which exerts its intracellular effects through activation of protein kinase A or the guanine nucleotide exchange protein 2A.

Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slices.

Many details of glucose-stimulated intracellular calcium changes in β cells during activation, activity, and deactivation, as well as their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that in islets, functional differences between individual cells are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some cells possibly coordinating the collective responses. To address the above with an emphasis on heterogeneity and describing the relations between classical physiological and functional network properties, we performed functional multicellular calcium imaging in mouse pancreas tissue slices over a wide range of glucose concentrations.

Socio-demographic and health factors drive the epidemic progression and should guide vaccination strategies for best COVID-19 containment.

We propose and study an epidemiological model on a social network that takes into account heterogeneity of the population and different vaccination strategies. In particular, we study how the COVID-19 epidemics evolves and how it is contained by different vaccination scenarios by taking into account data showing that older people, as well as individuals with comorbidities and poor metabolic health, and people coming from economically depressed areas with lower quality of life in general, are more likely to develop severe COVID-19 symptoms, and quicker loss of immunity and are therefore more prone to reinfection. Our results reveal that the structure and the spatial arrangement of subpopulations are important epidemiological determinants.

NMDA receptor inhibition increases, synchronizes, and stabilizes the collective pancreatic beta cell activity: Insights through multilayer network analysis.

NMDA receptors promote repolarization in pancreatic beta cells and thereby reduce glucose-stimulated insulin secretion. Therefore, NMDA receptors are a potential therapeutic target for diabetes. While the mechanism of NMDA receptor inhibition in beta cells is rather well understood at the molecular level, its possible effects on the collective cellular activity have not been addressed to date, even though proper insulin secretion patterns result from well-synchronized beta cell behavior.

Cataract Progression Associated with Modifications in Calcium Signaling in Human Lens Epithelia as Studied by Mechanical Stimulation.

Ca homeostasis and signaling disturbances are associated with lens pathophysiology and are involved in cataract formation. Here, we explored the spatiotemporal changes in Ca signaling in lens epithelial cells (LECs) upon local mechanical stimulation, to better understand the LECs' intercellular communication and its association with cataractogenesis. We were interested in if the progression of the cataract affects the Ca signaling and if modifications of the Ca homeostasis in LECs are associated with different cataract types.

Assessing Different Temporal Scales of Calcium Dynamics in Networks of Beta Cell Populations.

Beta cells within the pancreatic islets of Langerhans respond to stimulation with coherent oscillations of membrane potential and intracellular calcium concentration that presumably drive the pulsatile exocytosis of insulin. Their rhythmic activity is multimodal, resulting from networked feedback interactions of various oscillatory subsystems, such as the glycolytic, mitochondrial, and electrical/calcium components. How these oscillatory modules interact and affect the collective cellular activity, which is a prerequisite for proper hormone release, is incompletely understood.

Endogenous social distancing and its underappreciated impact on the epidemic curve.

Social distancing is an effective strategy to mitigate the impact of infectious diseases. If sick or healthy, or both, predominantly socially distance, the epidemic curve flattens. Contact reductions may occur for different reasons during a pandemic including health-related mobility loss (severity of symptoms), duty of care for a member of a high-risk group, and forced quarantine.

Mitochondrial Dysfunction in Pancreatic Alpha and Beta Cells Associated with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is a complex multifactorial disease of epidemic proportions. It involves genetic and lifestyle factors that lead to dysregulations in hormone secretion and metabolic homeostasis. Accumulating evidence indicates that altered mitochondrial structure, function, and particularly bioenergetics of cells in different tissues have a central role in the pathogenesis of type 2 diabetes mellitus.

Thermoregulation: A journey from physiology to computational models and the intensive care unit.

Thermoregulation plays a vital role in homeostasis. Many species of animals as well as humans have evolved various physiological mechanisms for body temperature control, which are characteristically flexible and enable a fine-tuned spatial and temporal regulation of body temperature in different environmental conditions and circumstances. Human beings normally maintain a core body temperature at around 37°C, and maintenance of this relatively high temperature is critical for survival.