154 results match your criteria: "Geneva Medical Center[Affiliation]"

Role of fatty acids in the pathogenesis of ß-cell failure and Type-2 diabetes.

Atherosclerosis

November 2024

Department of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland. Electronic address:

Pancreatic ß-cells are glucose sensors in charge of regulated insulin delivery to the organism, achieving glucose homeostasis and overall energy storage. The latter function promotes obesity when nutrient intake chronically exceeds daily expenditure. In case of ß-cell failure, such weight gain may pave the way for the development of Type-2 diabetes.

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GLUD1 determines murine muscle stem cell fate by controlling mitochondrial glutamate levels.

Dev Cell

November 2024

Pediatric Cancer Metabolism Laboratory, Children's Research Center, University of Zurich, 8032 Zurich, Switzerland; Division of Oncology, University Children's Hospital Zurich and Children's Research Center, University of Zurich, 8032 Zurich, Switzerland; Division of Human Genetics, Medical University Innsbruck, 6020 Innsbruck, Austria. Electronic address:

Muscle stem cells (MuSCs) enable muscle growth and regeneration after exercise or injury, but how metabolism controls their regenerative potential is poorly understood. We describe that primary metabolic changes can determine murine MuSC fate decisions. We found that glutamine anaplerosis into the tricarboxylic acid (TCA) cycle decreases during MuSC differentiation and coincides with decreased expression of the mitochondrial glutamate deaminase GLUD1.

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A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood. Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature.

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Provision of amino acids to the liver is instrumental for gluconeogenesis while it requires safe disposal of the amino group. The mitochondrial enzyme glutamate dehydrogenase (GDH) is central for hepatic ammonia detoxification by deaminating excessive amino acids toward ureagenesis and preventing hyperammonemia. The present study investigated the early adaptive responses to changes in dietary protein intake in control mice and liver-specific GDH KO mice (Hep-Glud1).

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Since the publication of the landmark thrombectomy trials in 2015, the field of endovascular therapy for ischemic stroke has been rapidly growing. The very low number needed to treat to provide functional benefits shown by the initial randomized trials has led clinicians and investigators to seek to translate the benefits of endovascular therapy to other patient subgroups. Even if the treatment effect is diminished, currently available data has provided sufficient information to extend endovascular therapy to large infarct core patients.

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Screening for new inhibitors of the human Mitochondrial Pyruvate Carrier and their effects on hepatic glucose production and diabetes.

Biochim Biophys Acta Gen Subj

December 2023

Department of Cell Physiology and Metabolism, University of Geneva Medical Center, rue Michel-Servet 1, 1206 Geneva, Switzerland; Faculty Diabetes Center, University of Geneva, 1206 Geneva, Switzerland. Electronic address:

Article Synopsis
  • * A screening of 1,200 FDA-approved drugs identified twelve potential inhibitors of the MPC, with Zaprinast and UK5099 showing the ability to reduce glucose production in liver cells, though they raised blood glucose levels in mice without gluconeogenic substrates.
  • * For effective antidiabetic treatments, new MPC inhibitors must specifically target liver glucose output while minimizing negative impacts on pyruvate metabolism in muscles and pancreatic cells to prevent unintended blood sugar spikes.
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Article Synopsis
  • The study identifies lysophosphatidylinositols (lysoPIs) as key lipid species that increase in the blood of prediabetic mice and diabetic patients, linked to the loss of pancreatic β-cells.
  • Increased lysoPIs correlate with markers of poor glycemic control, such as HbA1c and fasting glycemia, but not with insulin resistance or obesity in humans with type 2 diabetes.
  • The research indicates that lysoPIs enhance insulin secretion from pancreatic cells, suggesting a potential role in mitigating diabetes-related β-cell dysfunction.
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Postsurgical radiotherapy (RT) has been early proven to prevent local tumor recurrence, initially performed with whole brain RT (WBRT). Subsequent to disadvantageous cognitive sequalae for the patient and the broad distribution of modern linear accelerators, focal irradiation of the tumor has omitted WBRT in most cases. In many studies, the effectiveness of local RT of the resection cavity, either as single-fraction stereotactic radiosurgery (SRS) or hypo-fractionated stereotactic RT (hFSRT), has been demonstrated to be effective and safe.

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Generation of Insulin-Producing Multicellular Organoids.

Methods Mol Biol

December 2022

Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery, University of Geneva, Geneva, Switzerland.

Clinical islet transplantation (CIT) is an established noninvasive treatment for type I diabetes (T1D) and has demonstrated improved glycemic control, preventing the occurrence of severe hypoglycemia. However, CIT has several limitations, such as the need for multiple donors, lifelong immunosuppression, and suboptimal long-term graft function. Most of the transplanted islets are lost due to inflammation, ischemic damage, and delayed revascularization.

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Loss of Nexmif results in the expression of phenotypic variability and loss of genomic integrity.

Sci Rep

August 2022

Pediatric Endocrine and Diabetes Unit, Division of Development and Growth, Department of Pediatrics, Gynecology and Obstetrics, University Hospitals of Geneva, Children's University Hospital, 6, Rue Willy Donze, 1205, Geneva, Switzerland.

We identified two NEXMIF variants in two unrelated individuals with non-autoimmune diabetes and autistic traits, and investigated the expression of Nexmif in mouse and human pancreas and its function in pancreatic beta cells in vitro and in vivo. In insulin-secreting INS-1E cells, Nexmif expression increased strongly in response to oxidative stress. CRISPR Cas9-generated Nexmif knockout mice exhibited a reduced number of proliferating beta cells in pancreatic islets.

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Context: During an asymptomatic prediabetic state, the functional ß-cell mass decreases to a critical threshold, triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.

Objective: Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage.

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Muscle regeneration is essential for proper muscle homeostasis and relies primarily on muscle stem cells (MuSC). MuSC are maintained quiescent in their niche and can be activated following muscle injury. Using an in vitro model of primary human quiescent MuSC (called reserve cells, RC), we analyzed their Ca response following their activation by fetal calf serum and assessed the role of Ca in the processes of RC activation and migration.

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Hydrogen peroxide (HO) is a key defense component of host-microbe interaction. However, HO concentrations generated by immune cells or epithelia are usually insufficient for bacterial killing and rather modulate bacterial responses. Here, we investigated the impact of sublethal HO concentration on gene expression of BW25113 after 10 and 60 min of exposure.

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Bio-Engineering of Pre-Vascularized Islet Organoids for the Treatment of Type 1 Diabetes.

Transpl Int

March 2022

Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery, University of Geneva, Geneva, Switzerland.

Lack of rapid revascularization and inflammatory attacks at the site of transplantation contribute to impaired islet engraftment and suboptimal metabolic control after clinical islet transplantation. In order to overcome these limitations and enhance engraftment and revascularization, we have generated and transplanted pre-vascularized insulin-secreting organoids composed of rat islet cells, human amniotic epithelial cells (hAECs), and human umbilical vein endothelial cells (HUVECs). Our study demonstrates that pre-vascularized islet organoids exhibit enhanced function compared to native islets, and, most importantly, better engraftment and improved vascularization in a murine model.

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The need to consume adequate dietary protein to preserve physical function during ageing is well recognized. However, the effect of protein intakes on glucose metabolism is still intensively debated. During age-related estrogen withdrawal at the time of the menopause, it is known that glucose homeostasis may be impaired but the influence of dietary protein levels in this context is unknown.

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Aims/hypothesis: Chronic exposure of pancreatic beta cells to high glucose and fatty acids has been proposed to induce glucolipotoxicity. However, contradictory results suggest adaptations of the beta cells, which might be instrumental for partial preservation of the secretory response. In this context, we delineated the expression pattern of genes related to lipid pathways along with fat storage/mobilisation during glucose-stimulated insulin secretion.

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Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion.

Int J Mol Sci

December 2021

Department of Cell Physiology and Metabolism, Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, Switzerland.

Over the last decades, lipotoxicity and glucotoxicity emerged as established mechanisms participating in the pathophysiology of obesity-related type 2 diabetes in general, and in the loss of β-cell function in particular. However, these terms hold various potential biological processes, and it is not clear what precisely they refer to and to what extent they might be clinically relevant. In this review, we discuss the basis and the last advances of research regarding the role of free fatty acids, their metabolic intracellular pathways, and receptor-mediated signaling related to glucose-stimulated insulin secretion, as well as lipid-induced β-cell dysfunction.

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In 10-15% of cases of vestibular schwannoma (VS), age at diagnosis is 40 years or less. Little is known about the differences in natural history, surgical findings, and postoperative outcomes of such younger patients as compared to those of greater age. To analyze clinical and surgical and imaging data of a consecutive series of n = 50 patients with unilateral sporadic VS, aged 40 years or younger - separated in a very young group (15-30 years) and a moderately young group (31-40 years).

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Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins.

Int J Mol Sci

June 2021

Department of Basic Neuroscience, University of Geneva Medical Center, Rue Michel-Servet 1, 1206 Geneva, Switzerland.

The establishment of neuronal circuits requires neurons to develop and maintain appropriate connections with cellular partners in and out the central nervous system. These phenomena include elaboration of dendritic arborization and formation of synaptic contacts, initially made in excess. Subsequently, refinement occurs, and pruning takes places both at axonal and synaptic level, defining a homeostatic balance maintained throughout the lifespan.

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Electrophysiological correlates of improved executive function following EEG neurofeedback in adult attention deficit hyperactivity disorder.

Clin Neurophysiol

August 2021

Department of Psychiatry, University of Geneva, Geneva, Switzerland; Centre for Biomedical Imaging (CIBM) Lausanne-Geneva, Geneva, Switzerland; Functional Brain Mapping Laboratory, Department of Basic Neurosciences, University of Geneva, Geneva, Switzerland.

Objective: Event-related potentials (ERPs) are reported to be altered in relation to cognitive processing deficits in attention deficit hyperactivity disorder (ADHD). However, this evidence is mostly limited to cross-sectional data. The current study utilized neurofeedback (NFB) as a neuromodulatory tool to examine the ERP correlates of attentional and inhibitory processes in adult ADHD using a single-session, within-subject design.

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Respond of the different human cranial bones to pin-type head fixation device.

Acta Neurochir (Wien)

April 2021

Department of Neurosurgery, University of Geneva Medical Center & Faculty of Medicine, University of Geneva, Swiss Foundation for Innovation & Training in Surgery (SFITS), Rue Gabrielle-Perret-Gentil 4, Geneva, Switzerland.

Background: At this juncture, there is no consensus in the literature for the use and the safety of pin-type head holders in cranial procedures.

Methods: The present analysis of the bone response to the fixation of the instrument provides data to understand its impact on the entire skull as well as associated complications. An experimental study was conducted on fresh-frozen human specimens to analyze the puncture hole due to the fixation of each single pin of the pin-type head holder.

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Since deregulation of intracellular Ca can lead to intracellular trypsin activation, and stromal interaction molecule-1 (STIM1) protein is the main regulator of Ca homeostasis in pancreatic acinar cells, we explored the Ca signaling in 37 STIM1 variants found in three pancreatitis patient cohorts. Extensive functional analysis of one particular variant, p.E152K, identified in three patients, provided a plausible link between dysregulated Ca signaling within pancreatic acinar cells and chronic pancreatitis susceptibility.

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Mitochondrial Carriers Regulating Insulin Secretion Profiled in Human Islets upon Metabolic Stress.

Biomolecules

November 2020

Department of Cell Physiology and Metabolism & Faculty Diabetes Center, University of Geneva Medical Center, 1206 Geneva, Switzerland.

Chronic exposure of β-cells to nutrient-rich metabolic stress impairs mitochondrial metabolism and its coupling to insulin secretion. We exposed isolated human islets to different metabolic stresses for 3 days: 0.4 mM oleate or 0.

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