1. Study of a sensitive and selective electrochemical biosensor for glucose based on ▫$Bi_2Ru_2O_7$▫ pyrochlore clusters combined with MWCNTsJelena Isailović, Aleksandra Dapčević, Milan Žunić, Matjaž Finšgar, Kristijan Vidović, Nikola Tasić, Samo B. Hočevar, 2025, izvirni znanstveni članek Opis: The development of sensitive, selective, and reliable glucose biosensors remains a persistent challenge in clinical diagnostics. In this study, we exploited the advantageous (electro)catalytic properties of bismuth ruthenate (Bi2Ru2O7) pyrochlore clusters, known for their high surface activity and metallic-like conductivity, and the favorable physicochemical properties of multi-walled carbon nanotubes (MWCNTs) by combining them with glucose oxidase (GOD) in a sensitive and selective disposable glucose biosensor. The integration of Bi2Ru2O7 enabled an enhanced and more reproducible response of the biosensor along with fast and improved communication between the supporting electrode and the upper biosensing layer. The architecture of the biosensor involves the deposition of an MWCNT layer on a ferrocyanide-modified screen-printed carbon electrode (FCN-SPCE), followed by the application of a biorecognition layer including GOD and Bi2Ru2O7 clusters. The voltammetric biosensor showed excellent electroanalytical performance, capable of detecting low glucose concentrations with a detection limit of 40 μM along with a linear response across the examined concentration range of 1.0–20.0 mM. The biosensor exhibited good reproducibility with a relative standard deviation (RSD) of 1.2% and interference-free operation against several of the most common interfering compounds. The practical applicability of the biosensor was demonstrated by the determination of glucose in a real serum sample spiked with different concentrations of glucose.
Ključne besede: glucose sensor, glucose oxidase, Bi2Ru2O7 pyrochlore, multi-walled carbon nanotubes, voltammetry, serum
Objavljeno v DKUM: 20.03.2025; Ogledov: 0; Prenosov: 1
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2. Glucose-dependent activation, activity, and deactivation of beta cell networks in acute mouse pancreas tissue slicesAndraž Stožer, Maša Skelin, Marko Gosak, Lidija Križančić Bombek, Viljem Pohorec, Marjan Rupnik, Jurij Dolenšek, 2021, izvirni znanstveni članek Opis: Many details of glucose-stimulated intracellular calcium changes in [beta] 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. During activation, delays to activation of cells and any-cell-to-first-responder delays are shortened, and the sizes of simultaneously responding clusters increased with increasing glucose concentrations. Exactly the opposite characterized deactivation. The frequency of fast calcium oscillations during activity increased with increasing glucose up to 12 mM glucose concentration, beyond which oscillation duration became longer, resulting in a homogenous increase in active time. In terms of functional connectivity, islets progressed from a very segregated network to a single large functional unit with increasing glucose concentration. A comparison between classical physiological and network parameters revealed that the first-responders during activation had longer active times during plateau and the most active cells during the plateau tended to deactivate later. Cells with the most functional connections tended to activate sooner, have longer active times, and deactivate later. Our findings provide a common ground for recent differing views on [beta] cell heterogeneity and an important baseline for future studies of stimulus-secretion and intercellular coupling.
NEW & NOTEWORTHY: We assessed concentration-dependence in coupled [beta] cells, degree of functional heterogeneity, and uncovered possible specialized subpopulations during the different phases of the response to glucose at the level of many individual cells. To this aim, we combined acute mouse pancreas tissue slices with functional multicellular calcium imaging over a wide range from threshold (7 mM) and physiological (8 and 9 mM) to supraphysiological (12 and 16 mM) glucose concentrations, classical physiological, and advanced network analyses.
Ključne besede: beta cells, calcium imaging, glucose-dependence, network analysis
Objavljeno v DKUM: 15.10.2024; Ogledov: 0; Prenosov: 19
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3. Glucose-stimulated calcium dynamics in beta cells from male C57BL/6J, C57BL/6N, and NMRI mice : a comparison of activation, activity, and deactivation properties in tissue slicesViljem Pohorec, Lidija Križančić Bombek, Maša Skelin, Jurij Dolenšek, Andraž Stožer, 2022, izvirni znanstveni članek Opis: Although mice are a very instrumental model in islet beta cell research, possible phenotypic differences between strains and substrains are largely neglected in the scientific community. In this study, we show important phenotypic differences in beta cell responses to glucose between C57BL/6J, C57BL/6N, and NMRI mice, i.e., the three most commonly used strains. High-resolution multicellular confocal imaging of beta cells in acute pancreas tissue slices was used to measure and quantitatively compare the calcium dynamics in response to a wide range of glucose concentrations. Strain- and substrain-specific features were found in all three phases of beta cell responses to glucose: a shift in the dose-response curve characterizing the delay to activation and deactivation in response to stimulus onset and termination, respectively, and distinct concentration-encoding principles during the plateau phase in terms of frequency, duration, and active time changes with increasing glucose concentrations. Our results underline the significance of carefully choosing and reporting the strain to enable comparison and increase reproducibility, emphasize the importance of analyzing a number of different beta cell physiological parameters characterizing the response to glucose, and provide a valuable standard for future studies on beta cell calcium dynamics in health and disease in tissue slices.
Ključne besede: beta cell, mouse models, calcium imaging, glucose-dependence, tissue slice
Objavljeno v DKUM: 15.07.2024; Ogledov: 148; Prenosov: 22
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4. Probiotic mechanisms affecting glucose homeostasis : a scoping reviewMaša Pintarič, Tomaž Langerholc, 2022, pregledni znanstveni članek Opis: The maintenance of a healthy status depends on the coexistence between the host organism and the microbiota. Early studies have already focused on the nutritional properties of probiotics, which may also contribute to the structural changes in the gut microbiota, thereby affecting host metabolism and homeostasis. Maintaining homeostasis in the body is therefore crucial and is reflected at all levels, including that of glucose, a simple sugar molecule that is an essential fuel for normal cellular function. Despite numerous clinical studies that have shown the effect of various probiotics on glucose and its homeostasis, knowledge about the exact function of their mechanism is still scarce. The aim of our review was to select in vivo and in vitro studies in English published in the last eleven years dealing with the effects of probiotics on glucose metabolism and its homeostasis. In this context, diverse probiotic effects at different organ levels were highlighted, summarizing their potential mechanisms to influence glucose metabolism and its homeostasis. Variations in results due to different methodological approaches were discussed, as well as limitations, especially in in vivo studies. Further studies on the interactions between probiotics, host microorganisms and their immunity are needed.
Ključne besede: probiotic, mechanism, glucose, metabolism, homeostasis
Objavljeno v DKUM: 28.06.2024; Ogledov: 415; Prenosov: 15
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5. Telemonitoring of elderly with hypertension and type 2 diabetes at the primary care level : protocol for a multicentric randomized controlled pilot studyMatic Mihevc, Črt Zavrnik, Majda Mori-Lukančič, Tina Virtič, Valentina Prevolnik Rupel, Marija Petek Šter, Zalika Klemenc-Ketiš, Tonka Poplas-Susič, 2022, izvirni znanstveni članek Opis: Introduction: Arterial hypertension (AH) and type 2 diabetes (T2D) represent a significant burden for the public health system, with an exceptionally high prevalence in patients aged ≥65 years. This study aims to test the acceptability, clinical effectiveness, and cost-effectiveness of telemonitoring in elderly patients with AH and T2D at the primary care level.
Methods: A m ulti-centre, prospective, randomized, controlled t rial w ill be conducted. Patients a ged ≥ 65 y ears with AH and T2D will be randomized in a 1:1 proportion to a mHealth intervention or standard care group. Patients in the intervention group will measure their blood pressure (BP) twice weekly and blood glucose (BG) once monthly. The readings will be synchronously transmitted via a mobile application to the telemonitoring platform, where they will be reviewed by a general practitioner who will indicate changes in measurement regimen or carry out a teleconsultation. The primary endpoint will be a change in systolic BP (SBP) and glycated haemoglobin (HbA1c) relative to standard care up to 12 months after inclusion. Secondary endpoints will be a change in other observed clinical variables, quality-of-life indexes, and costs.
Expected results: Telemonitoring will be an acceptable method of care associated with significant reductions in SBP and HbA1c levels and an increase in quality-of-life indexes in the intervention group. However, the cost-effectiveness threshold (incremental cost-effectiveness ratio below €25,000/quality-adjusted life year) might not be reached.
Conclusion: This study will provide new evidence for scaling up telemonitoring network at the primary care level and modifying telemonitoring protocols to achieve the best clinical and cost-effective outcomes.
Ključne besede: mobile health, telemonitoring, blood pressure, blood glucose, HbA1c, aged, primary health care, costs
Objavljeno v DKUM: 27.06.2024; Ogledov: 178; Prenosov: 9
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6. Modeling the amino acid effect on glucagon secretion from pancreatic alpha cellsJan Zmazek, Vladimir Grubelnik, Rene Markovič, Marko Marhl, 2022, izvirni znanstveni članek Opis: Type 2 Diabetes Mellitus (T2DM) is a burdensome problem in modern society, and intensive research is focused on better understanding the underlying cellular mechanisms of hormone secretion for blood glucose regulation. T2DM is a bi-hormonal disease, and in addition to 100 years of increasing knowledge about the importance of insulin, the second hormone glucagon, secreted by pancreatic alpha cells, is becoming increasingly important. We have developed a mathematical model for glucagon secretion that incorporates all major metabolic processes of glucose, fatty acids, and glutamine as the most abundant postprandial amino acid in blood. In addition, we consider cAMP signaling in alpha cells. The model predictions quantitatively estimate the relative importance of specific metabolic and signaling pathways and particularly emphasize the important role of glutamine in promoting glucagon secretion, which is in good agreement with known experimental data.
Ključne besede: diabetes, hormone secretion, glucose, amino acid, cAMP
Objavljeno v DKUM: 21.05.2024; Ogledov: 169; Prenosov: 14
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7. Critical and supercritical spatiotemporal calcium dynamics in beta cellsMarko Gosak, Andraž Stožer, Rene Markovič, Jurij Dolenšek, Matjaž Perc, Marjan Rupnik, Marko Marhl, 2017, izvirni znanstveni članek Opis: 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, beta cells within islets form complex syncytia that are intrinsically nonlinear and highly heterogeneous. To study spatiotemporal calcium dynamics within these syncytia, we make use of computational modeling and confocal high-speed functional multicellular imaging. We show that model predictions are in good agreement with experimental data, especially if a high degree of heterogeneity in the intercellular coupling term is assumed. In particular, during the first few minutes after stimulation, the probability distribution of calcium wave sizes is characterized by a power law, thus indicating critical behavior. After this period, the dynamics changes qualitatively such that the number of global intercellular calcium events increases to the point where the behavior becomes supercritical. To better mimic normal in vivo conditions, we compare the described behavior during supraphysiological non-oscillatory stimulation with the behavior during exposure to a slightly lower and oscillatory glucose challenge. In the case of this protocol, we observe only critical behavior in both experiment and model. Our results indicate that the loss of oscillatory changes, along with the rise in plasma glucose observed in diabetes, could be associated with a switch to supercritical calcium dynamics and loss of beta cell functionality.
Ključne besede: beta cells, islets of Langerhans, self-organized criticality, intercellular dynamics, calcium waves, glucose oscillations, computational model, confocal calcium imaging
Objavljeno v DKUM: 23.01.2018; Ogledov: 1752; Prenosov: 396
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8. Magnetic field effects on redox potential of reduction and oxidation agentsMojca Božič, Lucija Črepinšek-Lipuš, Vanja Kokol, 2008, izvirni znanstveni članek Opis: Redox potentials of two reducing (sodium dithionite and glucose) and two oxidizing (hydrogen peroxide and sodium hypochlorite) agents were monitored at various concentrations and at different temperatures for 30-75 minutes after the exposure of their water solutions (glucose and hypochlorite solutions once; sodium dithionite and hydrogen peroxide solutions one, two and/or three-times) to the static magnetic field of flux density of 0.9 V s M-2 . The aim of the investigation was to suggest improvements, i.e., intensification and stability, of the reduction-oxidation ability of selected agents applicable in textile fibre processing, primarily bleaching and vat dyeing. Results of the experiments show that magnetic treatment (of solutions) raises both the reducing ability of glucose and the oxidation ability of hydrogen peroxide and sodium hypochlorite, promising some technological and economical benefits for the textile industry as well as forother fields of chemistry.
Ključne besede: magnetic water treatment, sodium dithionite, glucose, hydrogen peroxide, sodium hypochlorite, redox potential, textile vat processing
Objavljeno v DKUM: 05.07.2017; Ogledov: 1207; Prenosov: 129
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9. The relationship between membrane potential and calcium dynamics in glucose-stimulated beta cell syncytium in acute mouse pancreas tissue slicesJurij Dolenšek, Andraž Stožer, Maša Skelin, Evan Miller, Marjan Rupnik, 2013, izvirni znanstveni članek Opis: Oscillatory electrical activity is regarded as a hallmark of the pancreatic beta cell glucose-dependent excitability pattern. Electrophysiologically recorded membrane potential oscillations in beta cells are associated with in-phase oscillatory cytosolic calcium activity ([Ca2+]i) measured with fluorescent probes. Recent high spatial and temporal resolution confocal imaging revealed that glucose stimulation of beta cells in intact islets within acute tissue slices produces a [Ca2+]i change with initial transient phase followed by a plateau phase with highly synchronized [Ca2+]i oscillations. Here, we aimed to correlate the plateau [Ca2+]i oscillations with the oscillations of membrane potential using patch-clamp and for the first time high resolution voltage-sensitive dye based confocal imaging. Our results demonstrated that the glucose-evoked membrane potential oscillations spread over the islet in a wave-like manner, their durations and wave velocities being comparable to the ones for [Ca2+]i oscillations and waves. High temporal resolution simultaneous records of membrane potential and [Ca2+]i confirmed tight but nevertheless limited coupling of the two processes, with membrane depolarization preceding the [Ca2+]i increase. The potassium channel blocker tetraethylammonium increased the velocity at which oscillations advanced over the islet by several-fold while, at the same time, emphasized differences in kinetics of the membrane potential and the [Ca2+]i. The combination of both imaging techniques provides a powerful tool that will help us attain deeper knowledge of the beta cell network.
Ključne besede: glucose, pancreas, mice
Objavljeno v DKUM: 19.06.2017; Ogledov: 1323; Prenosov: 370
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10. Intracellular serotonin modulates insulin secretion from pancreatic ß-cells by protein serotonylationNils Paulmann, Maik Grohmann, Jörg-Peter Voigt, Bettina Bert, Jakob Vowinckel, Michael Bader, Maša Skelin, Marko Jevšek, Heidrun Fink, Marjan Rupnik, Diego Walther, 2009, izvirni znanstveni članek Opis: While serotonin (5-HT) co-localization with insulin in granules of pancreatic ß-cells was demonstrated more than three decades ago, its physiological role in the etiology of diabetes is stili unclear. We combined biochemical and electrophysiological analyses of mice selectively deficient in peripheral tryptophan hydroxylase (Tph1-/-) and 5-HT to show that intracellular 5-HT regulates insulin secretion. We found that these mice are diabetic and have an impaired insulin secretion due to the lack of 5-HT in the pancreas. The pharmacological restoration of peripheral 5-HT levels rescued the impaired insulin secretion in vivo. These findings were further evidenced by patch clamp experiments with isolated Tph1-/- ß-cells, which clearly showed that the secretory defect is downstream of Ca2+ -signaling and can be rescued by direct intracellular application of 5-HT via the clamp pipette. In elucidating the underlying mechanism further, we demonstrate the covalent coupling of 5-HT by transglutaminases during insulin exocytosis to two key players in insulin secretion, the small GTPases Rab3a and Rab27a. This renders them constitutively active in a receptor-independent signaling mechanism we have recently termed serotonylation. Concordantly, an inhibition of such activating serotonylation in ß-cells abates insulin secretion. We also observed inactivation of serotonylated Rab3a by enhanced proteasomal degradation, which is in line with the inactivation of other serotonylated GTPases. Our results demonstrate that 5-HT regulates insulin secretion by serotonylation of GTPases within pancreatic ß-cells and suggest that intracellular 5-HT functions in various microenvironments via this mechanism in concert with the known receptor-mediated signaling.
Ključne besede: insulin secretion, serotonin, insulin, glucose, diabetes mellitus, guanosine triphosphatase, exocytosis, pancreas
Objavljeno v DKUM: 16.06.2017; Ogledov: 2195; Prenosov: 207
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