- Pancreatic function and diabetes
- Diabetes and associated disorders
- Diabetes Management and Research
- Metabolism, Diabetes, and Cancer
- Receptor Mechanisms and Signaling
- Neural dynamics and brain function
- Gene Regulatory Network Analysis
- Diabetes Treatment and Management
- Adipose Tissue and Metabolism
- Pancreatitis Pathology and Treatment
- 3D Printing in Biomedical Research
- Cardiac Arrest and Resuscitation
- Photoreceptor and optogenetics research
- Thermal Regulation in Medicine
- Molecular Communication and Nanonetworks
- Neuroscience and Neuropharmacology Research
- Diet and metabolism studies
- stochastic dynamics and bifurcation
- Diet, Metabolism, and Disease
- Ion channel regulation and function
- Pancreatic and Hepatic Oncology Research
- Ion Transport and Channel Regulation
- Hepatocellular Carcinoma Treatment and Prognosis
- Cellular transport and secretion
- Respiratory Support and Mechanisms
University of Maribor
2016-2025
Czech Academy of Sciences, Institute of Physiology
2015-2023
Karolinska Institutet
2022
Medical University of Graz
2022
Open Society
2021
Pancreas Centre (Canada)
2017
Faculty (United Kingdom)
2015
University of Ljubljana
2008
The World Health Organization declared the coronavirus disease 2019 a pandemic on March 11th, pointing to over 118,000 cases in 110 countries and territories around world at that time. At time of writing this manuscript, number confirmed has been surging rapidly past half-million mark, emphasizing sustained risk further global spread. Governments are imposing various containment measures while healthcare system is bracing itself for tsunamis infected individuals will seek treatment. It...
The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes metabolism, membrane potential, intracellular calcium concentration, and exocytosis. potential consist of bursts spikes, silent phases between them being dominated by repolarization absence spikes. Assessing intra- intercellular at the multicellular level is possible ever-increasing detail, but our current ability to simultaneously resolve spikes from many cells remains limited...
We propose a network representation of electrically coupled beta cells in islets Langerhans. Beta are functionally connected on the basis correlations between calcium dynamics individual cells, obtained by means confocal laser-scanning imaging from acute mouse pancreas tissue slices. Obtained functional networks analyzed light known structural and physiological properties islets. Focusing temporal evolution under stimulation with glucose, we show that more correlated than non-stimulated...
In endocrine cells within islets of Langerhans calcium ions couple cell stimulation to hormone secretion. Since the advent modern fluorimetry, numerous in vitro studies employing primarily isolated mouse have investigated effects various secretagogues on cytoplasmic calcium, predominantly insulin-secreting beta cells. Due technical limitations, insights these are inherently limited a rather small subpopulation outermost The results also seem depend factors, like culture conditions and...
Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta cell glucose-dependent excitability pattern. Electrophysiologically recorded membrane potential oscillations in cells are associated with in-phase oscillatory cytosolic calcium ([Ca2+]i) measured fluorescent probes. Recent high spatial and temporal resolution confocal imaging revealed that glucose stimulation intact islets within acute tissue slices produces [Ca2+]i change initial transient phase followed by...
Many details of glucose-stimulated intracellular calcium changes in β cells during activation, activity, and deactivation, as well their concentration-dependence, remain to be analyzed. Classical physiological experiments indicated that islets, functional differences between individual are largely attenuated, but recent findings suggest considerable intercellular heterogeneity, with some possibly coordinating the collective responses. To address above an emphasis on heterogeneity describing...
Pancreatic islets are highly interconnected structures that produce pulses of insulin and other hormones, maintaining normal homeostasis glucose nutrients. Normal stimulus-secretion intercellular coupling essential to regulated secretory responses, these hallmarks known be altered in diabetes. In the current study, we used calcium imaging isolated human assess their collective behavior. The activity occurred form oscillations, was synchronized across different regions through waves,...
Collective beta cell activity in islets of Langerhans is critical for the supply insulin within an organism. Even though individual cells are intrinsically heterogeneous, presence intercellular coupling mechanisms ensures coordinated and a well-regulated exocytosis insulin. In order to get detailed insight into functional organization syncytium, we applied advanced analytical tools from realm complex network theory uncover connectivity pattern among composing intact islet. The procedure...
A coordinated functioning of beta cells within pancreatic islets is mediated by oscillatory membrane depolarization and subsequent changes in cytoplasmic calcium concentration. While gap junctions allow for intraislet information exchange, form complex syncytia that are intrinsically nonlinear highly heterogeneous. To study spatiotemporal dynamics these syncytia, we make use computational modeling confocal high-speed functional multicellular imaging. We show model predictions good agreement...
The release of peptide hormones is predominantly regulated by a transient increase in cytosolic Ca
Islets of Langerhans operate as multicellular networks in which several hundred β cells work synchrony to produce secretory pulses insulin, a hormone crucial for controlling metabolic homeostasis. Their collective rhythmic activity is facilitated by gap junctional coupling and affected their functional heterogeneity, but the details this robust coordinated behavior are still not fully understood. Recent advances imaging optogenetic photopharmacological strategies, well network science, have...
Within the islets of Langerhans, beta cells orchestrate synchronized insulin secretion, a pivotal aspect metabolic homeostasis. Despite inherent heterogeneity and multimodal activity individual cells, intercellular coupling acts as homogenizing force, enabling coordinated responses through propagation waves. Disruptions in this coordination are implicated irregular hallmark diabetes. Recently, innovative approaches, such integrating multicellular calcium imaging with network analysis, have...
Self-organized critical dynamics is assumed to be an attractive mode of functioning for several real-life systems and entails emergent activity in which the extent observables follows a power-law distribution. The hallmarks criticality have recently been observed plethora biological systems, including beta cell populations within pancreatic islets Langerhans. In present study, we systematically explored mechanisms that drive supercritical behavior networks coupled cells under different...
Beta cells within the pancreatic islets of Langerhans respond to stimulation with coherent oscillations membrane potential and intracellular calcium concentration that presumably drive pulsatile exocytosis insulin. Their rhythmic activity is multimodal, resulting from networked feedback interactions various oscillatory subsystems, such as glycolytic, mitochondrial, electrical/calcium components. How these modules interact affect collective cellular activity, which a prerequisite for proper...
NMDA receptors promote repolarization in pancreatic beta cells and thereby reduce glucose-stimulated insulin secretion. Therefore, are a potential therapeutic target for diabetes. While the mechanism of receptor inhibition is rather well understood at molecular level, its possible effects on collective cellular activity have not been addressed to date, even though proper secretion patterns result from well-synchronized cell behavior. The latter enabled by strong intercellular connectivity,...
Pancreatic beta cells are coupled excitable oscillators that synchronize their activity via different communication pathways. Their oscillatory manifests itself on multiple timescales and consists of bursting electrical activity, subsequent oscillations in the intracellular ${\mathrm{Ca}}^{2+}$, as well metabolism exocytosis. The coordination intricate multicellular level plays a key role regulation physiological pulsatile insulin secretion is incompletely understood. In this paper, we...