A5025586948- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Metabolism, Diabetes, and Cancer
- Diabetes and associated disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Muscle Physiology and Disorders
- MicroRNA in disease regulation
- Diabetes Management and Research
- Growth Hormone and Insulin-like Growth Factors
- Extracellular vesicles in disease
- Circular RNAs in diseases
- Diet, Metabolism, and Disease
- Diet and metabolism studies
- Peroxisome Proliferator-Activated Receptors
- Diabetes Treatment and Management
- Muscle metabolism and nutrition
- Chemokine receptors and signaling
- Exercise and Physiological Responses
- Fibroblast Growth Factor Research
- Pluripotent Stem Cells Research
- Calcium signaling and nucleotide metabolism
- RNA modifications and cancer
- Phagocytosis and Immune Regulation
- Protein Kinase Regulation and GTPase Signaling
- Regulation of Appetite and Obesity
Université de Strasbourg
2017-2025
Diabète et thérapie cellulaire
2018-2022
University of Geneva
2009-2020
Institute of Molecular Biology and Pathology
2013
HES-SO Genève
2011
Karolinska Institutet
2005-2008
Karolinska University Hospital
2006-2008
Université Claude Bernard Lyon 1
2001-2004
Inserm
2001-2004
Centre de Recherche en Nutrition Humaine Rhône-Alpes
2004
Most lifestyle-related chronic diseases are characterized by low-grade systemic inflammation and insulin resistance. Excessive tumor necrosis factor-α (TNF-α) concentrations have been implicated in the development of resistance, but direct evidence humans is lacking. Here, we demonstrate that TNF-α infusion healthy induces resistance skeletal muscle, without effect on endogenous glucose production, as estimated a combined euglycemic clamp stable isotope tracer method. directly impairs uptake...
Abstract Islets of patients with type 2 diabetes mellitus (T2DM) display features an inflammatory process including elevated levels the cytokine IL-1β, various chemokines, and macrophages. IL-1β is a master regulator inflammation, IL-1 receptor I (IL-1RI) blockage improves glycemia insulin secretion in humans T2DM high-fat-fed mice pointing to pivotal role IL-1RI activity intra-islet inflammation. Given association dyslipidemia T2DM, we tested whether free fatty acids (FFA) promote...
To understand better the defects in proximal steps of insulin signaling during type 2 diabetes, we used differentiated human skeletal muscle cells primary culture. When compared with from control subjects, myotubes established patients diabetes presented same as those previously evidenced vivo biopsies, including defective stimulation phosphatidylinositol (PI) 3-kinase activity, decreased association PI receptor substrate (IRS)-1 and reduced IRS-1 tyrosine phosphorylation stimulation. In...
Abstract We identified signaling pathways by which IL-6 regulates skeletal muscle differentiation and metabolism. Primary human cells were exposed to (25 ng/ml either acutely or for several days), small interfering RNA gene silencing was applied measure glucose fat Chronic exposure increased myotube fusion formation the mRNA expression of transporter 4, peroxisome proliferator activated receptor (PPAR)α, PPARδ, PPARγ, PPARγ coactivator 1, glycogen synthase, myocyte enhancer factor 2D,...
Interleukin-6 (IL-6) could be a possible mediator of insulin resistance. We investigated whether IL-6 inhibit signaling in human skeletal myotubes and suppressor cytokine 3 (SOCS-3) related to resistance vivo humans. inhibited induced SOCS-3 expression differentiated myotubes. mRNA levels were significantly increased the muscle type 2 diabetic patients compared with control subjects correlated reduced insulin-stimulated glucose uptake. In contrast, obese nondiabetic patients, despite similar...
Tumor necrosis factor-α (TNF-α) induces skeletal muscle insulin resistance by impairing signaling events involved in GLUT4 translocation. We tested whether mitogenic-activated protein kinase isoform 4 (MAP4K4) causes the TNF-α-induced negative regulation of extracellular signal-regulated kinase-1/2 (ERK-1/2), c-Jun NH2-terminal (JNK), and receptor substrate-1 (IRS-1) on pathway governing glucose metabolism. Using small interfering RNA (siRNA) to suppress expression MAP4K4 85% primary human...
Type 2 diabetes is characterized by insulin resistance with a relative deficiency in secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human rat) β-cells.Human cells were cultured for up to 24 h tumor necrosis factor (TNF)-α induce resistance, mRNA expression cytokines was analyzed compared controls (without TNF-α). Conditioned media collected candidate measured antibody array. Human rat β-cells used explore impact of...
Follistatin is a plasma protein recently reported to increase under conditions with negative energy balance, such as exercise and fasting in humans. Currently, the perception that circulating follistatin result of para/autocrine actions from various tissues. The large acute response suggests it may function an endocrine signal. We assessed origin regulation First, we arterial-to-venous difference over splanchnic bed at rest during healthy To evaluate manipulated glucagon-to-insulin ratio...
Circadian clocks are functional in all light-sensitive organisms, allowing an adaptation to the external world anticipation of daily environmental changes. In view potential role skeletal muscle clock regulation glucose metabolism, we aimed characterize circadian rhythms primary human myotubes and investigate their roles myokine secretion.We established a system for long-term bioluminescence recording differentiated myotubes, employing lentivector gene delivery Bmal1-luciferase...
Abstract Fine-tuning of insulin release from pancreatic β-cells is essential to maintain blood glucose homeostasis. Here, we report that secretion regulated by a circular RNA containing the lariat sequence second intron gene. Silencing this intronic in islets leads decrease expression key components secretory machinery β-cells, resulting impaired glucose- or KCl-induced and calcium signaling. The effect exerted at transcriptional level involves an interaction with RNA-binding protein TAR...
OBJECTIVE—Proinflammatory cytokines contribute to systemic low-grade inflammation and insulin resistance. Tumor necrosis factor (TNF)-α impedes signaling in target tissues. We determined the role of inhibitor nuclear factor-κB kinase (IKK)β TNF-α–induced impairments glucose metabolism skeletal muscle. RESEARCH DESIGN AND METHODS—Small interfering RNA (siRNA) was used silence IKKβ gene expression primary human muscle myotubes from nondiabetic subjects. siRNA silencing reduced protein 73% (P...
Malonyl coenzyme A (CoA) decarboxylase (MCD) is a key enzyme responsible for malonyl-CoA turnover and functions in the control of balance between lipid glucose metabolism. We utilized RNA interference (siRNA)-based gene silencing to determine direct role MCD on metabolic responses primary human skeletal muscle.We used siRNA silence expression cultured myotubes from healthy volunteers (seven male seven female) with no known disorders. Thereafter, we determined metabolism signal transduction...
The paired box homeodomain Pax6 is crucial for endocrine cell development and function plays an essential role in glucose homeostasis. Indeed, mutations of are associated with diabetic phenotype. Importantly, homozygous mutant mice characterized by markedly decreased β δ cells absent α cells. To better understand the critical that exerts glucagon-producing cells, we developed a model primary rat study transcriptional network adult differentiated generated Pax6-deficient using either specific...
Abstract Aim Pancreatic β‐cells are susceptible to inflammation, leading decreased insulin production/secretion and cell death. Previously, we have identified a novel triceps‐derived myokine, DECORIN, which plays pivotal role in skeletal muscle‐to‐pancreas interorgan communication. However, whether DECORIN can directly impact β‐cell function susceptibility inflammation remains unexplored. Methods The effect of was assessed sorted human rat islets from healthy type 2 diabetes (T2D) donors. We...
The development of intestinal goblet cell hyperplasia/hypertrophy during nematode infection involves the Th2 cytokines IL-4 and IL-13 via STAT6 activation. This is thought to play an important role in host protective immunity against infection. In this study we demonstrate that up-regulate specific product trefoil factor-3 (TFF3) from mucus-producing HT-29 CL.16E cells selected by adaptation methotrexate. Up-regulation TFF3 mRNA protein levels occurred a time- dose-dependent fashion was...
Obesity and type 2 diabetes present partially overlapping phenotypes with systemic inflammation as a common feature, raising the hypothesis that elevated cytokine levels may contribute to peripheral insulin resistance well decreased beta cell functional mass observed in diabetes. In healthy humans, TNF-alpha infusion induces skeletal muscle resistance. We now explore impact of on primary function underlying signaling pathways. Human rat cells were sorted by FACS cultured for 24 h +/- 20...
A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1) analogues induce proliferation rodent beta-cells. However, the proliferative capacity human beta-cells and its modulation by GLP-1 remain to be fully investigated. We therefore sought quantify adult vitro whether this affected analogue liraglutide. Human islets from 7 cadaveric organ donors were dispersed into single cells. Beta-cells purified FACS. Non-sorted cells enriched...