A5010645983- Pancreatic function and diabetes
- Diabetes and associated disorders
- Endoplasmic Reticulum Stress and Disease
- Phagocytosis and Immune Regulation
- Immune Cell Function and Interaction
- RNA regulation and disease
- Pancreatitis Pathology and Treatment
- NF-κB Signaling Pathways
- Metabolism, Diabetes, and Cancer
- Autophagy in Disease and Therapy
- Peptidase Inhibition and Analysis
- Diet, Metabolism, and Disease
- Diabetes Management and Research
- Adipokines, Inflammation, and Metabolic Diseases
- Cell death mechanisms and regulation
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Response and Inflammation
- Cardiac Structural Anomalies and Repair
- RNA modifications and cancer
- Adenosine and Purinergic Signaling
- Calcium signaling and nucleotide metabolism
- Diverse Scientific Research Studies
- RNA Interference and Gene Delivery
- MicroRNA in disease regulation
- Virus-based gene therapy research
Université Libre de Bruxelles
2013-2024
Ferrari (Italy)
2010
Massachusetts General Hospital
2010
Technical University of Denmark
2010
KU Leuven
2010
Harvard University
2010
Erasmus Hospital
2007
Vrije Universiteit Brussel
2000-2003
Aarhus University Hospital
2003
University of Colorado Health
2003
Free fatty acids (FFA) cause apoptosis of pancreatic beta-cells and might contribute to beta-cell loss in type 2 diabetes via the induction endoplasmic reticulum (ER) stress. We studied here molecular mechanisms implicated FFA-induced ER stress initiation INS-1E cells, FACS-purified primary human islets exposed oleate and/or palmitate. Treatment with saturated unsaturated FFA led differential signaling. Palmitate induced more markedly activated IRE1, PERK ATF6 pathways, owing a sustained...
Abstract Apoptosis is probably the main form of β-cell death in both type 1 diabetes mellitus (T1DM) and T2DM. In T1DM, cytokines contribute to destruction through nuclear factor-κB (NF-κB) activation. Previous studies suggested that T2DM high glucose free fatty acids (FFAs) are toxic also via NF-κB The aims this study were clarify whether common mechanisms involved FFA- cytokine-induced apoptosis determine TNFα, an adipocyte-derived cytokine, potentiates FFA toxicity enhanced was induced...
Cytokines and free radicals are mediators of β-cell death in type 1 diabetes. Under vitro conditions, interleukin-1β (IL-1β) + γ-interferon (IFN-γ) induce nitric oxide (NO) production apoptosis rodent human pancreatic β-cells. We have previously shown, by microarray analysis primary β-cells, that IL-1β IFN-γ decrease expression the mRNA encoding for sarcoendoplasmic reticulum pump Ca2+ ATPase 2b (SERCA2b) while inducing endoplasmic stress–related proapoptotic gene CHOP (C/EBP [CCAAT/enhancer...
Type 1 diabetes mellitus results from an autoimmune destruction of pancreatic β-cells. Cytokines, such as interleukin-1β and interferon-γ, are putative mediators immune-induced β-cell death and, under <i>in vitro</i>conditions, cause apoptosis. We have recently shown that + interferon-γ modifies the expression >200 genes in Several these targets for transcription factor nuclear factor-κB (NF-κB), subsequent experiments we showed NF-κB activation is mostly pro-apoptotic To identify...
Cytokine-induced β-cell death is an important event in the pathogenesis of type 1 diabetes. The transcription factor nuclear factor-κB (NF-κB) activated by interleukin-1β (IL-1β), and its activity promotes expression several genes, including pro- anti-apoptotic genes. To elucidate role cytokine (IL-1β + γ-interferon [IFN-γ])-induced NF-κB apoptosis, rat β-cells were infected with recombinant adenovirus AdIκB(SA)2, which contained a nondegradable mutant form inhibitory κB (IκB(SA)2, S32A...
Type 1 diabetes is an autoimmune disease resulting from the selective destruction of insulin-producing β-cells. Cytokines may contribute to pancreatic β-cell death in type diabetes. exposure interleukin (IL)-1β induces functional impairment, whereas culture for 6–9 days presence IL-1β and interferon (INF)-γ leads apoptosis. To clarify mechanisms involved these effects cytokines, we studied general pattern cytokine-induced gene expression Primary rat β-cells were fluorescence-activated cell...
Locally released cytokines contribute to β-cell dysfunction and apoptosis in type 1 diabetes. In vitro exposure of insulin-producing INS-1E cells the interleukin (IL)-1β + interferon (IFN)-γ leads a significant increase apoptosis. To characterize genetic networks implicated its dependence on nitric oxide (NO) production, we performed time-course microarray analysis cytokine-induced genes cells. were exposed duplicate IL-1β IFN-γ for six different time points (1, 2, 4, 8, 12, 24 h) with or...
1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) is an immune modulator that prevents experimental autoimmune diseases. Receptors for 1,25-(OH)(2)D(3) are present in pancreatic beta-cells, the target of assault nonobese diabetic (NOD) mice. The aim this study was to investigate vivo and vitro effects on beta-cell gene expression death correlate these findings diabetes development NOD When female mice were treated with (5 microg/kg per 2 d), there a decrease islet cytokine chemokine expression,...
OBJECTIVE The pathogenesis of type 1 diabetes has a strong genetic component. Genome-wide association scans recently identified novel susceptibility genes including the phosphatases PTPN22 and PTPN2. We hypothesized that PTPN2 plays direct role in β-cell demise assessed expression human islets rat primary clonal β-cells, besides evaluating its cytokine-induced signaling apoptosis. RESEARCH DESIGN AND METHODS mRNA protein was evaluated by real-time PCR Western blot. Small interfering (si)RNAs...
Cytokines, such as IL-1beta and TNF-alpha, contribute to pancreatic beta-cell death in type 1 diabetes mellitus. The transcription factor nuclear factor-kappaB (NF-kappaB) mediates cytokine-induced apoptosis. Paradoxically, NF-kappaB has mostly antiapoptotic effects other cell types. cellular actions of depend on the type, nature duration stimulus, periodicity, degree activity particular dimers involved. To clarify reasons behind proapoptotic beta-cells, we compared pattern activation...
Endoplasmic reticulum stress-mediated apoptosis may play an important role in the destruction of pancreatic beta-cells, thus contributing to development type 1 and 2 diabetes. One regulators endoplasmic cell death is CCAAT/enhancer binding protein (C/EBP) homologous (Chop). We presently studied molecular regulation Chop expression insulin-producing cells (INS-1E) response three pro-apoptotic stress-inducing agents, namely cytokines interleukin-1beta + interferon-gamma, free fatty acid...
Abstract Type 1 diabetes (T1D) results from β-cell destruction due to concerted action of both innate and adaptive immune responses. Pro-inflammatory cytokines, such as interleukin-1β interferon-γ, secreted by the cells invading islets Langerhans, contribute pancreatic death in T1D. Cytokine-induced endoplasmic reticulum (ER) stress plays a central role demise. ER can modulate autophagic response; however, no study addressed regulation autophagy during pathophysiology In this study, we...