A5033102611- Trace Elements in Health
- Pancreatic function and diabetes
- RNA regulation and disease
- Heavy Metal Exposure and Toxicity
- Iron Metabolism and Disorders
- Diabetes and associated disorders
- Genetics and Neurodevelopmental Disorders
- Diabetes Treatment and Management
- RNA Research and Splicing
- RNA modifications and cancer
- Aluminum toxicity and tolerance in plants and animals
- Viral Infections and Immunology Research
- Metabolism, Diabetes, and Cancer
- Child Nutrition and Water Access
- Pancreatitis Pathology and Treatment
- Cell death mechanisms and regulation
- Pharmacological Effects of Medicinal Plants
- CRISPR and Genetic Engineering
- Whipple's Disease and Interleukins
- Pediatric Hepatobiliary Diseases and Treatments
- Organic and Molecular Conductors Research
- Folate and B Vitamins Research
- Nicotinic Acetylcholine Receptors Study
- Drug Transport and Resistance Mechanisms
- Health, Environment, Cognitive Aging
Centre National de la Recherche Scientifique
2019-2022
Modélisation et Ingénierie des Systèmes Complexes Biologiques pour le Diagnostic
2019-2022
AstraZeneca (Sweden)
2018
Mellitech (France)
2006-2017
AstraZeneca (United Kingdom)
2014
Université Joseph Fourier
2002-2013
CEA Grenoble
2004-2012
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2001-2012
Institut Nanosciences et Cryogénie
2009-2012
Imperial College London
2009
SLC30A8, a novel member of the zinc transporter (ZnT) family, was identified by searching human genomic and expressed sequence tag (EST) databases with amino acid all known ZnT. The protein (369 acids) predicted from this gene, ZnT-8, contains six transmembrane domains histidine-rich loop between IV V, like other ZnT proteins. We demonstrated RT-PCR on cDNA libraries tissue extracts that ZnT-8 gene is solely transcribed in pancreas, mainly islets Langerhans. named cloned sequenced. Confocal...
OBJECTIVE Zinc ions are essential for the formation of hexameric insulin and hormone crystallization. A nonsynonymous single nucleotide polymorphism rs13266634 in SLC30A8 gene, encoding secretory granule zinc transporter ZnT8, is associated with type 2 diabetes. We describe effects deleting ZnT8 gene mice explore action at-risk allele. RESEARCH DESIGN AND METHODS Slc30a8 null were generated backcrossed at least twice onto a C57BL/6J background. Glucose tolerance measured by intraperitoneal...
Insulin-secreting pancreatic beta cells are exceptionally rich in zinc. In these cells, zinc is required for zinc-insulin crystallization within secretory vesicles. Secreted has also been proposed to be a paracrine and autocrine modulator of glucagon insulin secretion alpha respectively. However, little known about the molecular mechanisms underlying accumulation insulin-containing We previously identified pancreas-specific transporter, ZnT-8, which colocalized with cultured cells. this...
Zinc co-crystallizes with insulin in dense core secretory granules, but its role biosynthesis, storage and secretion is unknown. In this study we assessed the of zinc transporter ZnT8 using ZnT8-knockout ( −/− ) mice. Absence expression caused loss release upon stimulation exocytosis, normal rates content preserved glucose-induced release. Ultrastructurally, mature granules were rare beta cells replaced by immature, pale “progranules,” which larger than +/+ islets. When mice fed a control...
Mal de Meleda is an autosomal recessive inflammatory and keratotic palmoplantar skin disorder due to mutations in the ARS B gene, encoding for SLURP-1 (secreted mammalian Ly-6/uPAR-related protein 1). belongs Ly-6/uPAR superfamily of receptor secreted proteins, which participate signal transduction, immune cell activation or cellular adhesion. The high degree structural similarity between three fingers motif snake neurotoxins Lynx1 suggests that this interacts with neuronal acetylcholine...
The zinc(II) ion has recently been implicated in a number of novel functions and pathologies loci as diverse the brain, retina, small intestine, prostate, heart, pancreas, immune system. Zinc ions are required nutrient but elevated concentrations known to kill cells vitro. Paradoxical observations regarding zinc's effects have appeared frequently literature, often their physiological relevance is unclear. We found that for PC-12, HeLa HT-29 cell lines well primary cultures cardiac myocytes...
Intracellular zinc concentration and localization are strictly regulated by two main protein components, metallothioneins membrane transporters. In mammalian cells, transporters family involved in intracellular homeostasis: the uptake called SLC39 or Zip efflux SLC30 ZnT family. proteins members of cation diffusion facilitator (CDF) metal ion transporters.From genomic databanks analysis, we identified full-length sequences novel genes, SLC30A8 SLC30A10, extending to ten members. We used an...
During insulin secretion, pancreatic alpha-cells are exposed to Zn(2+) released from insulin-containing secretory granules. Although maintenance of homeostasis is critical for cell survival and glucagon very little known about Zn(2+)-transporting pathways the regulation in alpha-cells. To examine effect on secretion possible mechanisms controlling intracellular level ([Zn(2+)](i)), we employed a glucagon-producing line (alpha-TC6) mouse islets where non-beta-cells were identified using...
We evaluated the role of ATP-sensitive K⁺ (K(ATP)) channels, somatostatin, and Zn²⁺ in control glucagon secretion from mouse islets. Switching 1 to 7 mmol/L glucose inhibited release. Diazoxide did not reverse glucagonostatic effect glucose. Tolbutamide decreased at (G1) but stimulated it (G7). The reduced produced by high concentrations tolbutamide or diazoxide, disruption K(ATP) channels (Sur1(-/-) mice) G1 could be further G7. Removal somatostatin paracrine influence (Sst(-/-) mice...
Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D).
Genomewide association studies have linked a polymorphism in the zinc transporter 8 (Znt8) gene to higher risk of developing type 2 diabetes. Znt8 is highly expressed pancreatic β-cells where it involved regulation transport into granules. However, also other tissues including α-cells, its function as yet unknown. Previous work demonstrated that mice lacking globally were more susceptible diet-induced obesity (Lemaire et al., Proc Natl Acad Sci USA 106: 14872-14877, 2009; Nicolson Diabetes...
Beta-cells are extremely rich in zinc and homeostasis is regulated by transporter proteins. beta-cells sensitive to cytokines, interleukin-1beta (IL-1beta) has been associated with beta-cell dysfunction -death both type 1 2 diabetes. This study explores the regulation of transporters following cytokine exposure.The effects cytokines IL-1beta, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha) on gene expression were measured INS-1-cells rat pancreatic islets. Being more...
Hypoxic damage complicates islet isolation for transplantation and may contribute to beta cell failure in type 2 diabetes. Polymorphisms the SLC30A8 gene, encoding secretory granule zinc transporter 8 (ZnT8), influence diabetes risk, conceivably by modulating cytosolic Zn(2+) levels. We have therefore explored role of ZnT8 response hypoxia pancreatic cells.
In clinical practice, differentiating Bipolar Disorder (BD) from unipolar depression is a challenge due to the depressive symptoms, which are core presentations of both disorders. This misdiagnosis during episodes results in delay proper treatment and poor management their condition. first step, using A-to-I RNA editome analysis, we discovered 646 variants (366 genes) differentially edited between depressed patients healthy volunteers discovery cohort 57 participants. After stringent...