A5006602429- Pancreatic function and diabetes
- Mitochondrial Function and Pathology
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- ATP Synthase and ATPases Research
- Metabolomics and Mass Spectrometry Studies
- Calcium signaling and nucleotide metabolism
- Fungal and yeast genetics research
- Cellular transport and secretion
- Diabetes and associated disorders
- Diabetes Management and Research
- Sirtuins and Resveratrol in Medicine
- RNA Interference and Gene Delivery
- Electrochemical sensors and biosensors
- Microtubule and mitosis dynamics
- 3D Printing in Biomedical Research
- Photoreceptor and optogenetics research
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Neuroscience and Neural Engineering
- Biochemical Acid Research Studies
- Bioinformatics and Genomic Networks
École Polytechnique Fédérale de Lausanne
2014-2024
Nestlé (Switzerland)
2013-2023
Nestlé (France)
2016
University of Geneva
2009-2011
University of Alberta
2011
Unidades Centrales Científico-Técnicas
2008
Consejo Superior de Investigaciones Científicas
2008
Yale University
2003-2004
University of Basel
2000-2001
Centre National de la Recherche Scientifique
2000
Abstract Pathologic alterations in podocytes lead to failure of an essential component the glomerular filtration barrier and proteinuria chronic kidney diseases. Elevated levels saturated free fatty acid (FFA) are harmful various tissues, implemented progression diabetes its complications such as diabetic nephropathy. Here, we investigated molecular mechanism palmitate cytotoxicity cultured mouse podocytes. Incubation with dose-dependently increased cytosolic mitochondrial reactive oxygen...
Barrier integrity is central to the maintenance of healthy immunological homeostasis. Impaired skin barrier function linked with enhanced allergen sensitization and development diseases such as atopic dermatitis (AD), which can precede other allergic disorders, for example, food allergies asthma. Epidemiological evidence indicates that children suffering from have lower levels dietary fibre-derived short-chain fatty acids (SCFA). Using an experimental model AD-like inflammation, we report a...
Medium-chain triglycerides have been used as part of a ketogenic diet effective in reducing epileptic episodes. The health benefits the derived medium-chain fatty acids (MCFAs) are thought to result from stimulation liver ketogenesis providing fuel for brain. We tested whether MCFAs direct effects on energy metabolism induced pluripotent stem cell-derived human astrocytes and neurons. Using single-cell imaging, we observed an acute pronounced reduction mitochondrial electrical potential...
Mitochondria capture and subsequently release Ca(2+) ions, thereby sensing shaping cellular signals. The uniporter MCU mediates uptake, whereas NCLX (mitochondrial Na/Ca exchanger) LETM1 (leucine zipper-EF-hand-containing transmembrane protein 1) were proposed to exchange against Na(+) or H(+), respectively. Here we study the role of these ion exchangers in mitochondrial extrusion Ca(2+)-metabolic coupling. Both proteins expressed HeLa cells mitochondria. rate efflux, measured with a...
Skp1p–cullin–F-box protein (SCF) complexes are ubiquitin-ligases composed of a core complex including Skp1p, Cdc53p, Hrt1p, the E2 enzyme Cdc34p, and one multiple F-box proteins which thought to provide substrate specificity complex. Here we show that Rcy1p is required for recycling v-SNARE Snc1p in Saccharomyces cerevisiae. localized areas polarized growth, this localization its CAAX box an intact actin cytoskeleton. interacted with Skp1p vivo F-box-dependent manner, both deletion F loss...
In Saccharomyces cerevisiae, endocytic material is transported through different membrane-bound compartments before it reaches the vacuole. a screen for mutants that affect membrane trafficking along pathway, we have identified novel mutant disrupted gene YJL204c renamed RCY1 (recycling 1). Deletion of leads to an early block in pathway intersection with vacuolar protein sorting pathway. Mutation accumulation enlarged compartment contains t-SNARE Tlg1p and lies close areas cell expansion....
Mitochondria form filamentous networks that undergo continuous fission/fusion. In the pancreatic beta-cells, mitochondria are essential for transduction of signals linking nutrient metabolism to insulin granule exocytosis. Here we have studied mitochondrial in insulinoma cell line INS-1E, primary rat and human beta-cells. We further investigated impact fission/fusion on metabolism-secretion coupling INS-1E cells. Overexpression hFis1 caused dramatic fragmentation, whereas Mfn1 evoked...
To evaluate whether healthy or diabetic adult mice can tolerate an extreme loss of pancreatic α-cells and how this sudden massive depletion affects β-cell function blood glucose homeostasis.We generated a new transgenic model allowing near-total α-cell removal specifically in mice. Massive ablation was triggered normally grown animals upon diphtheria toxin (DT) administration. The metabolic status these assessed 1) physiologic conditions, 2) situation requiring glucagon action, 3) after...
Sec3p is a component of the exocyst complex that tethers secretory vesicles to plasma membrane at exocytic sites in preparation for fusion. Unlike all other structural genes, SEC3 not essential growth. Cells lacking grow and secrete surprisingly well 25 degrees C; however, late markers secretion, such as vesicle marker Sec4p subunit Sec8p, localize more diffusely within bud. Furthermore, sec3Delta cells are strikingly round relative wild-type unable form pointed mating projections response...
Using the ROS (reactive oxygen species)-sensitive fluorescent dyes dichlorodihydrofluorescein and dihydroethidine, previous studies yielded opposite results about glucose regulation of oxidative stress in insulin-secreting pancreatic β-cells. In present paper, we used ratiometric proteins HyPer roGFP1 (redox-sensitive green protein 1) targeted to mitochondria [mt-HyPer (mitochondrial HyPer)/mt-roGFP1 roGFP1)] monitor glucose-induced changes mitochondrial hydrogen peroxide concentration...
In pancreatic β-cells, ATP acts as a signaling molecule initiating plasma membrane electrical activity linked to Ca(2+) influx, which triggers insulin exocytosis. The mitochondrial uniporter (MCU) mediates uptake into the organelle, where energy metabolism is further stimulated for sustained second phase secretion. Here, we have studied contribution of MCU regulation oxidative phosphorylation and metabolism-secretion coupling in intact permeabilized clonal β-cells well rat islets. Knockdown...
Background and Purpose Quinic acid (QA) is an abundant natural compound from plant sources which may improve metabolic health. However, little attention has been paid to its effects on pancreatic beta‐cell functions, contribute the control of health by lowering blood glucose. Strategies targeting signal transduction are a new approach for diabetes treatment. This study investigated efficacy QA stimulate function basic molecular machinery metabolism–secretion coupling. Experimental Approach...
Inorganic phosphate (Pi) plays an important role in cell signaling and energy metabolism. In insulin-releasing cells, Pi transport into mitochondria is essential for the generation of ATP, a factor metabolism-secretion coupling. Elevated concentrations, however, can have toxic effects various types. The underlying molecular mechanisms are poorly understood. Here, we investigated effect on secretory function apoptosis INS-1E clonal β-cells rat pancreatic islets. extracellular (1~5 mM)...
Abstract A robust and reproducible method for culturing monolayers of adherent well-spread primary islet cells on glass coverslips is required detailed imaging studies by super-resolution live-cell microscopy. Guided an observation that dispersed spread adhere well surfaces in neuronal co-culture form a monolayer connected cells, we demonstrate the absence neurons, well-defined surface coatings combined with components culture media collectively support attachment growth human or rat as...
High levels of Ca2+ in the endoplasmic reticulum (ER), established by sarco/endoplasmic ATPase (SERCA), are required for protein folding and cell signalling. Excessive ER release or decreased SERCA activity induces unfolded accumulation stress pancreatic β-cells, leading to defective insulin secretion diabetes. Here we have investigated consequences enhancing uptake on β-cell survival function.The effects activator, CDN1163, homeostasis, expression, mitochondrial activities, secretion,...
The exocyst is an octameric protein complex required to tether secretory vesicles exocytic sites and retain ER tubules at the apical tip of budded cells. Unlike other five genes, SEC3, SEC5, EXO70 are not essential for growth or secretion when either upstream activator rab, Sec4p, downstream SNARE-binding component, Sec1p, overproduced. Analysis suppressed sec3Δ, sec5Δ, exo70Δ strains demonstrates that corresponding proteins confer differential effects on vesicle targeting inheritance. Sec3p...