A5018493361- Glycogen Storage Diseases and Myoclonus
- Pancreatic function and diabetes
- Metabolism, Diabetes, and Cancer
- Genetics and Neurodevelopmental Disorders
- Lysosomal Storage Disorders Research
- Lipid metabolism and biosynthesis
- Alcohol Consumption and Health Effects
- Endoplasmic Reticulum Stress and Disease
- Diet, Metabolism, and Disease
- Cancer, Hypoxia, and Metabolism
- Metabolism and Genetic Disorders
- Liver Disease Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Wnt/β-catenin signaling in development and cancer
- Mitochondrial Function and Pathology
- Neurological disorders and treatments
- Carbohydrate Chemistry and Synthesis
- Cancer therapeutics and mechanisms
- Microtubule and mitosis dynamics
- Ubiquitin and proteasome pathways
- Protein Tyrosine Phosphatases
- Biochemical and Structural Characterization
- Blood Coagulation and Thrombosis Mechanisms
- Diabetes Management and Research
- Neurological diseases and metabolism
Institute for Research in Biomedicine
2009-2020
Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
2009-2015
Instituto de Salud Carlos III
2014-2015
Universitat de Barcelona
2000-2015
Barcelona Biomedical Research Park
2002
Universidad Autónoma de Madrid
1994-1998
Consejo Superior de Investigaciones Científicas
1996-1997
Centro de Biología Molecular Severo Ochoa
1994-1997
When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription enzymes glucose metabolism. Here we show that regulates expression muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity Response Element within its promoter. gene correlated with significant accumulation exposed to...
Lafora disease is a fatal neurodegenerative condition characterized by the accumulation of abnormal glycogen inclusions known as bodies. It an autosomal recessive disorder caused mutations in either laforin or malin gene. To study whether primarily responsible for neurodegeneration disease, we generated knockout mice with impaired (totally partially) synthesis. These animals did not show increase markers neurodegeneration, impairments electrophysiological properties hippocampal synapses, nor...
Abstract Lafora disease (LD) is caused by mutations in either the laforin or malin gene. The hallmark of accumulation polyglucosan inclusions called Bodies (LBs). Malin knockout (KO) mice present accumulations several brain areas, as do patients LD. These structures are abundant cerebellum and hippocampus. Here, we report a large increase glycogen synthase (GS) these mice, which enzyme accumulates LBs. Our study focused on hippocampus where, under physiological conditions, astrocytes...
Lafora progressive myoclonus epilepsy (LD) is a fatal autosomal recessive neurodegenerative disorder characterized by the presence of glycogen-like intracellular inclusions called bodies. LD caused mutations in two genes, EPM2A and EPM2B, encoding respectively laforin, dual-specificity protein phosphatase, malin, an E3 ubiquitin ligase. Previously, we others have suggested that interactions between laforin PTG (a regulatory subunit type 1 phosphatase) malin are critical pathogenesis LD....
The liver responds to an increase in blood glucose levels the postprandial state by uptake of and conversion glycogen. Liver glycogen synthase (GYS2), a key enzyme synthesis, is controlled complex interplay between allosteric activator glucose-6-phosphate (G6P) reversible phosphorylation through kinase-3 glycogen-associated form protein phosphatase 1. Here, we initially performed mutagenesis analysis identified residue (Arg582) required for activation GYS2 G6P. We then used Arg582Ala knockin...
Abstract Under physiological conditions, most neurons keep glycogen synthase (GS) in an inactive form and do not show detectable levels of glycogen. Nevertheless, aberrant accumulation is a hallmark patients suffering from Lafora disease or other polyglucosan disorders. Although these diseases are associated with mutations genes involved metabolism, the role remains elusive. Here, we generated mouse fly models expressing active GS to force neuronal We present evidence that progressive...
Abstract The mechanisms that allow breast cancer (BCa) cells to metabolically sustain rapid growth are poorly understood. Here we report BCa dependent on a mechanism supply precursors for intracellular lipid production derived from extracellular sources and the endothelial lipase (LIPG) fulfils this function. LIPG expression allows import of precursors, thereby contributing proliferation. stands out as an essential component metabolic adaptations cells, not normal tissue, must undergo...
Significance The body stores excess blood glucose as glycogen, a sugary substance that contains up to 55,000 molecules joined together chain, mostly in liver and muscle cells. Conversion of glycogen these cells plays an important role regulating levels. Glycogen ensures we don’t run out fuel during prolonged exercise. To make from sugar, need two enzymes: glycogenin synthase. Glycogenin kick starts the process by first linking itself string residues then recruiting synthase elaborate this...
Changes in the intracellular distribution of liver glycogen synthase (GS) might constitute a new regulatory mechanism for activity this enzyme at cellular level. Our previous studies indicated that incubation isolated hepatocytes with glucose activated GS and resulted its translocation from homogeneous cytosolic to cell periphery. These also suggested relationship insoluble elements cytoskeleton, particular actin. Here we show different experimental model allows analysis phenomenon long-term...
Eukaryotic glycogen synthase activity is regulated by reversible phosphorylation at multiple sites. Of the two GS isoforms found in mammals, muscle enzyme (muscle synthase) has received more attention and relative importance of every known site control its intracellular distribution been previously addressed. We have analyzed impact dephosphorylation homologous sites liver (LGS) isoform. Serine residues these were replaced non-phosphorylatable alanine residues, singly or pairs, resultant LGS...
Changes in the intracellular distribution of liver glycogen synthase (GS) might constitute a new regulatory mechanism for activity this enzyme at cellular level. Our previous studies indicated that incubation isolated hepatocytes with glucose activated GS and resulted its translocation from homogeneous cytosolic to cell periphery. These also suggested relationship insoluble elements cytoskeleton, particular actin. Here we show different experimental model allows analysis phenomenon long-term...
Glycogen is the main source of glucose for many biological events. However, this molecule may have other functions, including those that deleterious effects on cells. The rate-limiting enzyme in glycogen synthesis synthase (GS). It encoded by two genes, GYS1, expressed muscle (muscle synthase, MGS) and tissues, GYS2, primarily liver (liver LGS). Expression GS its activity been widely studied tissues. To date, it not clear which isoform responsible role testis. Using RT-PCR, Western blot...
In this study, we tested the efficacy of increasing liver glycogen synthase to improve blood glucose homeostasis. The overexpression wild-type in rats had no effect on homeostasis either fed or fasted state. contrast, expression a constitutively active mutant form enzyme caused significant lowering former but not latter Moreover, it markedly enhanced clearance when were challenged with load. Hepatic stores overexpressing activated state and response an oral load showed net decline during...
Glucose 6-phosphate (Glc-6-P) produced in cultured hepatocytes by direct phosphorylation of glucose or gluconeogenesis from dihydroxyacetone (DHA) was equally effective activating glycogen synthase (GS). However, accumulation higher incubated with than those treated DHA. This difference attributed to decreased futile cycling through GS and phosphorylase (GP) the glucose-treated hepatocytes, owing partial inactivation GP induced glucose. Our results indicate that gluconeogenic pathway...
Understanding how glucose metabolism is finely regulated at molecular and cellular levels in the liver critical for knowing its relationship to related pathologies, such as diabetes. In order gain insight into regulation of metabolism, we studied liver-expressed isoforms aldolase B fructose-1,6-bisphosphatase-1 (FBPase-1), key enzymes gluconeogenesis, analysing their localization hepatocytes under different metabolic conditions protein-protein interaction vitro vivo. We observed that...