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Modeling the amino acid effect on glucagon secretion from pancreatic alpha cells
Jan 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: 20; Prenosov: 0
.pdf Celotno besedilo (1,82 MB)
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Age-related changes in lipid and glucose levels associated with drug use and mortality : an observational study
Rene Markovič, Vladimir Grubelnik, Helena Blažun Vošner, Peter Kokol, Matej Završnik, Karmen Janša, Marjeta Zupet, Jernej Završnik, Marko Marhl, 2022, izvirni znanstveni članek

Opis: Background: The pathogenesis of type 2 diabetes mellitus is complex and still unclear in some details. The main feature of diabetes mellitus is high serum glucose, and the question arises of whether there are other statistically observable dysregulations in laboratory measurements before the state of hyperglycemia becomes severe. In the present study, we aim to examine glucose and lipid profiles in the context of age, sex, medication use, and mortality. Methods: We conducted an observational study by analyzing laboratory data from 506,083 anonymized laboratory tests from 63,606 different patients performed by a regional laboratory in Slovenia between 2008 and 2019. Laboratory data-based results were evaluated in the context of medication use and mortality. The medication use database contains anonymized records of 1,632,441 patients from 2013 to 2018, and mortality data were obtained for the entire Slovenian population. Results: We show that the highest percentage of the population with elevated glucose levels occurs approximately 20 years later than the highest percentage with lipid dysregulation. Remarkably, two distinct inflection points were observed in these laboratory results. The first inflection point occurs at ages 55 to 59 years, corresponding to the greatest increase in medication use, and the second coincides with the sharp increase in mortality at ages 75 to 79 years. Conclusions: Our results suggest that medications and mortality are important factors affecting population statistics and must be considered when studying metabolic disorders such as dyslipidemia and hyperglycemia using laboratory data.
Ključne besede: diabetes, metabolic syndrome, hematological data, aging
Objavljeno v DKUM: 21.05.2024; Ogledov: 18; Prenosov: 0
.pdf Celotno besedilo (2,12 MB)
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Blood-based mRNA tests as emerging diagnostic tools for personalised medicine in breast cancer
Helena Sabina Čelešnik, Uroš Potočnik, 2023, pregledni znanstveni članek

Ključne besede: breast cancer, peripheral blood, diagnostic assay, mRNA test, cancer screening
Objavljeno v DKUM: 20.05.2024; Ogledov: 13; Prenosov: 0
.pdf Celotno besedilo (430,71 KB)
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Gene ontology analysis highlights biological processes influencing responsiveness to biological therapy in psoriasis
Martina Krušič, Gregor Jezernik, Uroš Potočnik, 2023, izvirni znanstveni članek

Objavljeno v DKUM: 09.05.2024; Ogledov: 50; Prenosov: 3
.pdf Celotno besedilo (316,44 KB)
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Self-organization of enzyme-catalyzed reactions studied by the maximum entropy production principle
Andrej Dobovišek, Marko Vitas, Tina Blaževič, Rene Markovič, Marko Marhl, Aleš Fajmut, 2023, izvirni znanstveni članek

Opis: The self-organization of open reaction systems is closely related to specific mechanisms that allow the export of internally generated entropy from systems to their environment. According to the second law of thermodynamics, systems with effective entropy export to the environment are better internally organized. Therefore, they are in thermodynamic states with low entropy. In this context, we study how self-organization in enzymatic reactions depends on their kinetic reaction mechanisms. Enzymatic reactions in an open system are considered to operate in a non-equilibrium steady state, which is achieved by satisfying the principle of maximum entropy production (MEPP). The latter is a general theoretical framework for our theoretical analysis. Detailed theoretical studies and comparisons of the linear irreversible kinetic schemes of an enzyme reaction in two and three states are performed. In both cases, in the optimal and statistically most probable thermodynamic steady state, a diffusion-limited flux is predicted by MEPP. Several thermodynamic quantities and enzymatic kinetic parameters, such as the entropy production rate, the Shannon information entropy, reaction stability, sensitivity, and specificity constants, are predicted. Our results show that the optimal enzyme performance may strongly depend on the number of reaction steps when linear reaction mechanisms are considered. Simple reaction mechanisms with a smaller number of intermediate reaction steps could be better organized internally and could allow fast and stable catalysis. These could be features of the evolutionary mechanisms of highly specialized enzymes.
Ključne besede: enzymes, kinetic data analysis, steady state, self-organization, maximum entropy production
Objavljeno v DKUM: 08.05.2024; Ogledov: 75; Prenosov: 2
.pdf Celotno besedilo (2,57 MB)
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The synthesis, surface analysis, and cellular response of titania and titanium oxynitride nanotube arrays prepared on TiAl6V4 for potential biomedical applications
Katja Andrina Kravanja, Luka Suhadolnik, Marjan Bele, Uroš Maver, Jan Rožanc, Željko Knez, Maša Knez Marevci, Matjaž Finšgar, 2023, izvirni znanstveni članek

Opis: Titania nanotubes are gaining prominence in the biomedical field as implant materials due to their mechanical durability, nano-rough properties, and positive influence on cellular response. This work aimed to synthesize titania and titanium oxynitride (TieOeN) nano- tubular arrays on TiAl6V4 substrates using an anodic oxidation process followed by annealing in air or by additional nitridation in NH3 atmosphere. Different nanotubular layers of unique morphology and structure were fabricated and investigated using advanced surface analysis and biocompatibility tests. In-depth surface analysis was per- formed by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), 3D profilometry, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and time-of-flight secondary ion mass spectroscopy (ToF-SIMS). Cell testing using adipose- derived mesenchymal stem cells and human fetal osteoblasts demonstrated good cell viability, high proliferative capacity, and a favorable overall effect on cell morphology for the TieOeN nanotubes.
Ključne besede: surface analysis, XPS, AFM, tandem ToF-SIMS, titania nanotubes, Ti-O-N nanotubes, anodization
Objavljeno v DKUM: 07.05.2024; Ogledov: 57; Prenosov: 2
.pdf Celotno besedilo (8,31 MB)
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