Imperial College London

DrGabrielaDa Silva Xavier

Faculty of MedicineDepartment of Medicine

Non-Clinical Lecturer in Cell Biology/Physiology
 
 
 
//

Contact

 

+44 (0)20 7594 3358g.dasilva-xavier

 
 
//

Location

 

326ICTEM buildingHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

56 results found

Fletcher RS, Ratajczak J, Doig CL, Oakey LA, Callingham R, Da Silva Xavier G, Garten A, Elhassan YS, Redpath P, Migaud ME, Philp A, Brenner C, Canto C, Lavery GGet al., 2017, Nicotinamide riboside kinases display redundancy in mediating nicotinamide mononucleotide and nicotinamide riboside metabolism in skeletal muscle cells., Mol Metab, Vol: 6, Pages: 819-832

OBJECTIVE: Augmenting nicotinamide adenine dinucleotide (NAD+) availability may protect skeletal muscle from age-related metabolic decline. Dietary supplementation of NAD+ precursors nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) appear efficacious in elevating muscle NAD+. Here we sought to identify the pathways skeletal muscle cells utilize to synthesize NAD+ from NMN and NR and provide insight into mechanisms of muscle metabolic homeostasis. METHODS: We exploited expression profiling of muscle NAD+ biosynthetic pathways, single and double nicotinamide riboside kinase 1/2 (NRK1/2) loss-of-function mice, and pharmacological inhibition of muscle NAD+ recycling to evaluate NMN and NR utilization. RESULTS: Skeletal muscle cells primarily rely on nicotinamide phosphoribosyltransferase (NAMPT), NRK1, and NRK2 for salvage biosynthesis of NAD+. NAMPT inhibition depletes muscle NAD+ availability and can be rescued by NR and NMN as the preferred precursors for elevating muscle cell NAD+ in a pathway that depends on NRK1 and NRK2. Nrk2 knockout mice develop normally and show subtle alterations to their NAD+ metabolome and expression of related genes. NRK1, NRK2, and double KO myotubes revealed redundancy in the NRK dependent metabolism of NR to NAD+. Significantly, these models revealed that NMN supplementation is also dependent upon NRK activity to enhance NAD+ availability. CONCLUSIONS: These results identify skeletal muscle cells as requiring NAMPT to maintain NAD+ availability and reveal that NRK1 and 2 display overlapping function in salvage of exogenous NR and NMN to augment intracellular NAD+ availability.

JOURNAL ARTICLE

Nguyen-Tu M-S, Leclerc I, da Silva-Xavier G, Rutter GAet al., 2016, Role of the type 2 diabetes GWAS gene TCF7L2 in LKB1-mediated regulation of insulin secretion in the murine beta cell, 52nd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S169-S169, ISSN: 0012-186X

CONFERENCE PAPER

Semplici F, Mondragon A, Macintyre B, Madeyski-Bengston K, Persson-Kry A, Barr S, Ramne A, Marley A, McGinty J, French P, Soedling H, Yokosuka R, Gaitan J, Lang J, Migrenne-Li S, Philippe E, Herrera PL, Magnan C, Xavier GDS, Rutter GAet al., 2016, Cell type-specific deletion in mice reveals roles for PAS kinase in insulin and glucagon production, DIABETOLOGIA, Vol: 59, Pages: 1938-1947, ISSN: 0012-186X

JOURNAL ARTICLE

Mitchell RK, Mondragon A, Chen L, Mcginty JA, French PM, Ferrer J, Thorens B, Hodson DJ, Rutter GA, Xavier GDSet al., 2015, Selective disruption of Tcf7l2 in the pancreatic beta cell impairs secretory function and lowers beta cell mass, HUMAN MOLECULAR GENETICS, Vol: 24, Pages: 1390-1399, ISSN: 0964-6906

JOURNAL ARTICLE

Sun G, Da Silva Xavier G, Gorman T, Priest C, Solomou A, Hodson DJ, Foretz M, Viollet B, Herrera PL, Parker HE, Reimann FM, Gribble FM, Migrenne S, Magnan CN, Marley AE, Rutter GAet al., 2015, LKB1 and AMPKα1 are required in pancreatic alpha cells for the normal regulation of glucagon secretion and responses to hypoglycemia, Molecular Metabolism, Vol: 4, Pages: 277-286, ISSN: 2212-8778

Aims/Hypothesis: Glucagon release from pancreatic alpha cells is required for normal glucose homoeostasis and is dysregulated in both Type 1 and Type 2 diabetes. The tumour suppressor LKB1 (STK11) and the downstream kinase AMP-activated protein kinase (AMPK), modulate cellular metabolism and growth, and AMPK is an important target of the anti-hyperglycaemic agent metformin. While LKB1 and AMPK have emerged recently as regulators of beta cell mass and insulin secretion, the role of these enzymes in the control of glucagon production invivo is unclear. Methods: Here, we ablated LKB1 (αLKB1KO), or the catalytic alpha subunits of AMPK (αAMPKdKO, -α1KO, -α2KO), selectively in ~45% of alpha cells in mice by deleting the corresponding flox'd alleles with a preproglucagon promoter (. PPG) Cre. Results: Blood glucose levels in male αLKB1KO mice were lower during intraperitoneal glucose, aminoimidazole carboxamide ribonucleotide (AICAR) or arginine tolerance tests, and glucose infusion rates were increased in hypoglycemic clamps (p<0.01). αLKB1KO mice also displayed impaired hypoglycemia-induced glucagon release. Glucose infusion rates were also elevated (p<0.001) in αAMPKα1 null mice, and hypoglycemia-induced plasma glucagon increases tended to be lower (p=0.06). Glucagon secretion from isolated islets was sensitized to the inhibitory action of glucose in αLKB1KO, αAMPKdKO, and -α1KO, but not -α2KO islets. Conclusions/Interpretation: An LKB1-dependent signalling cassette, involving but not restricted to AMPKα1, is required in pancreatic alpha cells for the control of glucagon release by glucose.

JOURNAL ARTICLE

Zatyka M, Xavier GDS, Bellomo EA, Leadbeater W, Astuti D, Smith J, Michelangeli F, Rutter GA, Barrett TGet al., 2015, Sarco(endo)plasmic reticulum ATPase is a molecular partner of Wolfram syndrome 1 protein, which negatively regulates its expression, HUMAN MOLECULAR GENETICS, Vol: 24, Pages: 814-827, ISSN: 0964-6906

JOURNAL ARTICLE

Locke JM, Xavier GDS, Dawe HR, Rutter GA, Harries LWet al., 2014, Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion, DIABETOLOGIA, Vol: 57, Pages: 122-128, ISSN: 0012-186X

JOURNAL ARTICLE

Mondragon A, Davidsson D, Kyriakoudi S, Bertling A, Gomes-Faria R, Cohen P, Rothery S, Chabosseau P, Rutter GA, Xavier GDSet al., 2014, Divergent Effects of Liraglutide, Exendin-4, and Sitagliptin on Beta-Cell Mass and Indicators of Pancreatitis in a Mouse Model of Hyperglycaemia, PLOS ONE, Vol: 9, ISSN: 1932-6203

JOURNAL ARTICLE

Xavier GDS, Bellomo EA, McGinty JA, French PM, Rutter GAet al., 2013, Animal Models of GWAS-Identified Type 2 Diabetes Genes, JOURNAL OF DIABETES RESEARCH, ISSN: 2314-6745

JOURNAL ARTICLE

Xavier GDS, Mondragon A, Sun G, Chen L, McGinty JA, French PM, Rutter GAet al., 2012, Abnormal glucose tolerance and insulin secretion in pancreas-specific Tcf7l2-null mice, DIABETOLOGIA, Vol: 55, Pages: 2667-2676, ISSN: 0012-186X

JOURNAL ARTICLE

da Silva Xavier G, 2012, Protein kinases and pancreatic islet function, Protein kinases, Editors: da Silva Xavier, Publisher: Intech, ISBN: 978-953-51-0640-1

BOOK CHAPTER

da Silva Xavier G, Others M, 2012, Protein Kinases, Online, Publisher: InTech, ISBN: 978-953-51-0640-1

Proteins are the work horses of the cell. As regulators of protein function, protein kinases are involved in the control of cellular functions via intricate signalling pathways, allowing for fine tuning of physiological functions. This book is a collaborative effort, with contribution from experts in their respective fields, reflecting the spirit of collaboration - across disciplines and borders - that exists in modern science. Here, we review the existing literature and, on occasions, provide novel data on the function of protein kinases in various systems. We also discuss the implications of these findings in the context of disease, treatment, and drug development.

BOOK

Dominguez V, Raimondi C, Somanath S, Bugliani M, Loder MK, Edling CE, Divecha N, da Silva-Xavier G, Marselli L, Persaud SJ, Turner MD, Rutter GA, Marchetti P, Falasca M, Maffucci Tet al., 2011, Class II Phosphoinositide 3-Kinase Regulates Exocytosis of Insulin Granules in Pancreatic beta Cells, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 4216-4225, ISSN: 0021-9258

JOURNAL ARTICLE

Locke JM, Xavier GDS, Rutter GA, Harries LWet al., 2011, An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes, DIABETOLOGIA, Vol: 54, Pages: 3078-3082, ISSN: 0012-186X

JOURNAL ARTICLE

Meur G, Qian Q, Xavier GDS, Pullen TJ, Tsuboi T, McKinnon C, Fletcher L, Tavare JM, Hughes S, Johnson P, Rutter GAet al., 2011, Nucleo-cytosolic Shuttling of FoxO1 Directly Regulates Mouse Ins2 but Not Ins1 Gene Expression in Pancreatic Beta Cells (MIN6), JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 286, Pages: 13647-13656, ISSN: 0021-9258

JOURNAL ARTICLE

Pullen TJ, Xavier GDS, Kelsey G, Rutter GAet al., 2011, miR-29a and miR-29b Contribute to Pancreatic beta-Cell-Specific Silencing of Monocarboxylate Transporter 1 (Mct1), MOLECULAR AND CELLULAR BIOLOGY, Vol: 31, Pages: 3182-3194, ISSN: 0270-7306

JOURNAL ARTICLE

Xavier GDS, Farhan H, Kim H, Caxaria S, Johnson P, Hughes S, Bugliani M, Marselli L, Marchetti P, Birzele F, Sun G, Scharfmann R, Rutter J, Siniakowicz K, Weir G, Parker H, Reimann F, Gribble FM, Rutter GAet al., 2011, Per-arnt-sim (PAS) domain-containing protein kinase is downregulated in human islets in type 2 diabetes and regulates glucagon secretion, DIABETOLOGIA, Vol: 54, Pages: 819-827, ISSN: 0012-186X

JOURNAL ARTICLE

An R, Xavier GDS, Semplici F, Vakhshouri S, Hao H-X, Rutter J, Pagano MA, Meggio F, Pinna LA, Rutter GAet al., 2010, Pancreatic and duodenal homeobox 1 (PDX1) phosphorylation at serine-269 is HIPK2-dependent and affects PDX1 subnuclear localization, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 399, Pages: 155-161, ISSN: 0006-291X

JOURNAL ARTICLE

Noordeen NA, Khera TK, Sun G, Longbottom ER, Pullen TJ, Xavier GDS, Rutter GA, Leclerc Iet al., 2010, Carbohydrate-Responsive Element-Binding Protein (ChREBP) Is a Negative Regulator of ARNT/HIF-1 beta Gene Expression in Pancreatic Islet beta-Cells, DIABETES, Vol: 59, Pages: 153-160, ISSN: 0012-1797

JOURNAL ARTICLE

Rutter GA, Pullen TJ, 2010, miR-29a, miR-29b and miR-124 contribute to pancreatic beta cell specific silencing of monocarboxylate transporter 1 (Mct1/Slc16a1), 46th Annual Meeting of the European-Association-for-the- Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S35-S36, ISSN: 0012-186X

CONFERENCE PAPER

Sun G, Tarasov AI, McGinty J, McDonald A, Xavier GDS, Gorman T, Marley A, French PM, Parker H, Gribble F, Reimann F, Prendiville O, Carzaniga R, Viollet B, Leclerc I, Rutter GAet al., 2010, Ablation of AMP-activated protein kinase alpha 1 and alpha 2 from mouse pancreatic beta cells and RIP2.Cre neurons suppresses insulin release in vivo, DIABETOLOGIA, Vol: 53, Pages: 924-936, ISSN: 0012-186X

JOURNAL ARTICLE

Voronina SG, Barrow SL, Simpson AWM, Gerasimenko OV, Xavier GDS, Rutter GA, Petersen OH, Tepikin AVet al., 2010, Dynamic Changes in Cytosolic and Mitochondrial ATP Levels in Pancreatic Acinar Cells, GASTROENTEROLOGY, Vol: 138, Pages: 1976-U111, ISSN: 0016-5085

JOURNAL ARTICLE

Xavier GDS, Sun G, Qian Q, Rutter GA, Leclerc Iet al., 2010, ChREBP regulates Pdx-1 and other glucose-sensitive genes in pancreatic beta-cells, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol: 402, Pages: 252-257, ISSN: 0006-291X

JOURNAL ARTICLE

Nicolson TJ, Bellomo EA, Wijesekara N, Loder MK, Baldwin JM, Gyulkhandanyan AV, Koshkin V, Tarasov AI, Carzaniga R, Kronenberger K, Taneja TK, Xavier GDS, Libert S, Froguel P, Scharfmann R, Stetsyuk V, Ravassard P, Parker H, Gribble FM, Reimann F, Sladek R, Hughes SJ, Johnson PRV, Masseboeuf M, Burcelin R, Baldwin SA, Liu M, Lara-Lemus R, Arvan P, Schuit FC, Wheeler MB, Chimienti F, Rutter GAet al., 2009, Insulin Storage and Glucose Homeostasis in Mice Null for the Granule Zinc Transporter ZnT8 and Studies of the Type 2 Diabetes-Associated Variants, DIABETES, Vol: 58, Pages: 2070-2083, ISSN: 0012-1797

JOURNAL ARTICLE

Xavier GDS, Loder MK, McDonald A, Tarasov AI, Carzaniga R, Kronenberger K, Barg S, Rutter GAet al., 2009, TCF7L2 Regulates Late Events in Insulin Secretion From Pancreatic Islet beta-Cells, DIABETES, Vol: 58, Pages: 894-905, ISSN: 0012-1797

JOURNAL ARTICLE

Barrow SL, Voronina SG, Xavier GDS, Chvanov MA, Longbottom RE, Gerasimenko OV, Petersen OH, Rutter GA, Tepikin AVet al., 2008, ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile, PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, Vol: 455, Pages: 1025-1039, ISSN: 0031-6768

JOURNAL ARTICLE

Loder MK, Xavier GDS, McDonald A, Rutter GAet al., 2008, TCF7L2 controls insulin gene expression and insulin secretion in mature pancreatic beta-cells, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 36, Pages: 357-359, ISSN: 0300-5127

JOURNAL ARTICLE

Zatyka M, Ricketts C, Xavier GDS, Minton J, Fenton S, Hofmann-Thiel S, Rutter GA, Barrett TGet al., 2008, Sodium-potassium ATPase beta 1 subunit is a molecular partner of Wolframin, an endoplasmic reticulum protein involved in ER stress, HUMAN MOLECULAR GENETICS, Vol: 17, Pages: 190-200, ISSN: 0964-6906

JOURNAL ARTICLE

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00503833&limit=30&person=true