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Lipotoxicity in a vicious cycle of pancreatic beta cell exhaustion
Vladimir Grubelnik, Jan Zmazek, Matej Završnik, Marko Marhl, 2022, izvirni znanstveni članek

Opis: Hyperlipidemia is a common metabolic disorder in modern society and may precede hyperglycemia and diabetes by several years. Exactly how disorders of lipid and glucose metabolism are related is still a mystery in many respects. We analyze the effects of hyperlipidemia, particularly free fatty acids, on pancreatic beta cells and insulin secretion. We have developed a computational model to quantitatively estimate the effects of specific metabolic pathways on insulin secretion and to assess the effects of short- and long-term exposure of beta cells to elevated concentrations of free fatty acids. We show that the major trigger for insulin secretion is the anaplerotic pathway via the phosphoenolpyruvate cycle, which is affected by free fatty acids via uncoupling protein 2 and proton leak and is particularly destructive in long-term chronic exposure to free fatty acids, leading to increased insulin secretion at low blood glucose and inadequate insulin secretion at high blood glucose. This results in beta cells remaining highly active in the “resting” state at low glucose and being unable to respond to anaplerotic signals at high pyruvate levels, as is the case with high blood glucose. The observed fatty-acid-induced disruption of anaplerotic pathways makes sense in the context of the physiological role of insulin as one of the major anabolic hormones.
Ključne besede: diabetes, insulin secretion, lipids, PEP cycle, uncoupling proteins, mitochondrial dysfunction
Objavljeno v DKUM: 20.05.2024; Ogledov: 36; Prenosov: 2
.pdf Celotno besedilo (2,47 MB)
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Lipid layers on polyelectrolyte multilayer supports
Martin Fischlechner, Markus Zaulig, Stefan Meyer, Irina Estrela-Lopis, Luis Cuéllar, Joseba Irigoyen, Paula Pescador, Milan Brumen, Paul Messner, Sergio Moya, Edwin Donath, 2008, izvirni znanstveni članek

Opis: The mechanism of formation of supported lipid layers from phosphatidylcholine and phosphatidylserine vesicles in solution on polyelectrolyte multilayers was studied by a variety of experimental techniques. The interaction of zwitterionic and acidic lipid vesicles, as well as their mixtures, with polyelectrolyte supports was followed in real time by micro-gravimetry. The fabricated lipid-polyelectrolyte composite structures on top of multilayer coated colloidal particles were characterized by flow cytometry and imaging techniques. Lipid diffusion over the macroscopic scale was quantified by fluorescence recovery after photobleaching, and the diffusion was related to layer connectivity. The phospholipid-polyelectrolyte binding mechanism was investigated by infrared spectroscopy. A strong interaction of polyelectrolyte primary amino groups with phosphate and carboxyl groups of the phospholipids, leading to dehydration, was observed. Long-range electrostatic attraction was proven to be essential for vesicle spreading and rupture. Fusion of lipid patches into a homogeneous bilayer required lateral mobility of the lipids on the polyelectrolyte support. The binding of amino groups to the phosphate group of the zwitterionic lipids was too weak to induce vesicle spreading, but sufficient for strong adsorption. Only the mixture of phosphatidylcholine and phosphatidylserine resulted in the spontaneous formation of bilayers on polyelectrolyte multilayers. The adsorption of phospholipids onto multilayers displaying quarternary ammonium polymers produced a novel 3D lipid polyelectrolyte structure on colloidal particles.
Ključne besede: biophysics, lipids, lipid layers, electrolytes, multilayer supports
Objavljeno v DKUM: 07.06.2012; Ogledov: 1776; Prenosov: 73
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Supercritical fluid adsorption and desorption of lipids on various adsorbents
Mojca Škerget, Željko Knez, 2007, izvirni znanstveni članek

Opis: In present work the feasibility of using supercritical fluid chromatography (SFC) for separation of free fatty acids (FFA) and triglycerides has been examined. Lipids such as oleic acid and sunflower oil (containing 96% of triglycerides) were used; adsorption and desorption on adsorbents such as silica gel and neusilin using supercritical $CO_2$ as mobile phase was investigated. The experiments were performed at 40 °C and in the pressure range from 13 to 30 MPa. Adsorption kinetic lines were determined by analysingbreakthrough curves. Several parameters such as rate of adsorption and desorption, loading, desorbed quantity and diffusion coefficients in solid phase were calculated.
Ključne besede: supercritical fluid chromatography, lipids, oleic acid, triglycerides, adsorption, desorption
Objavljeno v DKUM: 31.05.2012; Ogledov: 2496; Prenosov: 111
.pdf Celotno besedilo (167,88 KB)
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