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Glycogen Metabolism (glycogen + metabolism)
Selected AbstractsMitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contractionACTA PHYSIOLOGICA, Issue 3 2001U. Widegren Exercise has numerous growth and metabolic effects in skeletal muscle, including changes in glycogen metabolism, glucose and amino acid uptake, protein synthesis and gene transcription. However, the mechanism(s) by which exercise regulates intracellular signal transduction to the transcriptional machinery in the nucleus, thus modulating gene expression, is largely unknown. This review will provide insight on potential intracellular signalling mechanisms by which muscle contraction/exercise leads to changes in gene expression. Mitogen-activated protein kinase (MAPK) cascades are associated with increased transcriptional activity. The MAPK family members can be separated into distinct parallel pathways including the extracellular signal-regulated kinase (ERK) 1/2, the stress-activated protein kinase cascades (SAPK1/JNK and SAPK2/p38) and the extracellular signal-regulated kinase 5 (ERK5). Acute exercise elicits signal transduction via MAPK cascades in direct response to muscle contraction. Thus, MAPK pathways appear to be potential physiological mechanisms involved in the exercise-induced regulation of gene expression in skeletal muscle. [source] Molecular characterisation of GSD III subjects and identification of six novel mutations in AGL,,HUMAN MUTATION, Issue 6 2002S. Lucchiari Abstract Deficiency of amylo-1,6-glucosidase, 4-,-glucanotransferase enzyme (AGL or glycogen debranching enzyme) is causative of Glycogen Storage Disease type III, a rare autosomal recessive disorder of glycogen metabolism. The disease has been demonstrated to show clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different subjects. The aim of this study was the molecular characterisation of eight unrelated patients from an ethnically heterogeneous population (six Italians, one from India and another one from Tunisia). We describe six novel mutations responsible for the disease (C234R, R675W, 2547delG, T38A, W1327X, IVS6 +3 A>G) and the presence in two Italian subjects of a splice variant (IVS21+1 G>A) already described elsewhere. This last one is confirmed to be the most frequent mutation among the Italian patients come to our observation, accounting for 28% of 21 patients. One subject was found to be a compound heterozygous. Our data confirm the substantial genetic heterogeneity of this disease. Consequently, the strategy of mutation finding based on screening of recurrent common mutations is limited, as far as regards Italian GSD III patients, to check for the presence of IVS21+1 G>A. © 2002 Wiley-Liss, Inc. [source] Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammationMEDICINAL RESEARCH REVIEWS, Issue 4 2002Ana Martinez Abstract Glycogen synthase kinase 3 (GSK-3) was initially described as a key enzyme involved in glycogen metabolism, but is now known to regulate a diverse array of cell functions. Two forms of the enzyme, GSK-3, and GSK-3,, have been previously identified. Small molecules inhibitors of GSK-3 may, therefore, have several therapeutic uses, including the treatment of neurodegenerative diseases, diabetes type II, bipolar disorders, stroke, cancer, and chronic inflammatory disease. As there is lot of recent literature dealing with the involvement of GSK-3 in the molecular pathways of different diseases, this review is mainly focused on the new GSK-3 inhibitors discovered or specifically developed for this enzyme, their chemical structure, synthesis, and structure,activity relationships, with the aim to provide some clues for the future optimization of these promising drugs. © 2002 Wiley Periodicals, Inc. Med Res Rev, 22, No. 4, 373,384, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/med.10011 [source] Is In Vivo Nuclear Magnetic Resonance Spectroscopy Currently a Quantitative Method for Whole-body Carbohydrate Metabolism?NUTRITION REVIEWS, Issue 10 2000Elizabeth Murphy M.D., Ph.D. In vivo nuclear magnetic resonance (NMR) spectroscopy is a powerful tool for noninvasive metabolic research. NMR studies of tissue glycogen metabolism and glucose utilization have generated results with major implications for normal glucose homeostasis and the pathophysiology of type 2 diabetes mellitus. A key question for clinicians and physiologists reading these highly technical studies is: How accurate for whole-body carbohydrate metabolism is NMR spectroscopy? We review this topic and discuss technical, metabolic, and interpretive factors that may limit quantitative accuracy of this modality. We conclude that seeing is not yet believing regarding in vivo NMR spectroscopy; there are still important limitations to quantification of whole-body carbohydrate metabolism. [source] Partial phenotypic correction and immune tolerance induction to enzyme replacement therapy after hematopoietic stem cell gene transfer of ,-glucosidase in Pompe diseaseTHE JOURNAL OF GENE MEDICINE, Issue 4 2009Gaëlle Douillard-Guilloux Abstract Background Glycogen storage disease type II (GSDII) or Pompe disease is an inherited disease of glycogen metabolism caused by a lack of functional lysosomal acid ,-glucosidase (GAA). Affected individuals store glycogen in lysosomes resulting in fatal hypertrophic cardiomyopathy and respiratory failure in the most severe form. Even if enzyme replacement therapy (ERT) has already proven some efficacy, its results remain heterogeneous in skeletal muscle, especially in cross reactive immunological material (CRIM)-negative patients. We investigated for the first time the use of hematopoietic stem cell (HSC) gene therapy in a murine model of GSDII. Methods Deficient HSC were transduced with a lentiviral vector expressing human GAA or enhanced green fluorescent protein (GFP) under the control of the retroviral MND promoter and transplanted into lethally irradiated GSDII mice. Animals were then subjected to an ERT protocol for 5 weeks and monitored for metabolic correction and GAA-induced immune reaction. Results GAA was expressed as a correctly processed protein, allowing a complete enzymatic correction in transduced deficient cells without toxicity. Seventeen weeks after transplantation, a partial restoration of the GAA enzymatic activity was observed in bone marrow and peripheral blood cells of GSDII mice, allowing a significant glycogen clearance in skeletal muscle. ERT induced a robust antibody response in GFP-transplanted mice, whereas no immune reaction could be detected in GAA-transplanted mice. Conclusions Lentiviral vector-mediated HSC gene therapy leads to a partial metabolic correction and induces a tolerance to ERT in GSDII mice. This strategy could enhance the efficacy of ERT in CRIM-negative Pompe patients. Copyright © 2009 John Wiley & Sons, Ltd. [source] GSK3,: role in therapeutic landscape and development of modulatorsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2010S Phukan Glycogen synthase kinase-3 beta (GSK3,) is a multifunctional serine/threonine kinase which was originally identified as a regulator of glycogen metabolism. It plays a key role in the regulation of numerous signalling pathways including cellular process such as cell cycle, inflammation and cell proliferation. Over the last few years there is a considerable rise in the number of journals and patents publication by different workers worldwide. Many pharmaceutical companies are focusing on GSK3, as a therapeutic target for the treatment of disease conditions. The present review is focused on signalling pathways of different disease conditions where GSK3, is implicated. In this review, we present a comprehensive map of GSK3, signalling pathways in disease physiologies. Structural analysis of GSK3, along with molecular modelling reports from numerous workers are reviewed in context of design and development of GSK3, inhibitors. Patent landscape of the small molecule modulators is profiled. The chemo space for small molecule modulators extracted from public and proprietary Kinase Chembiobase for GSK3, are discussed. Compounds in different clinical phases of discovery are analysed. The review ends with the overall status of this important therapeutic target and challenges in development of its modulators. [source] Liver glycogen metabolism during short-term insulin-induced hypoglycemia in fed ratsCELL BIOCHEMISTRY AND FUNCTION, Issue 7 2008Simoni Obici Abstract The activities of glycogen phosphorylase and synthase during infusions of glucagon, isoproterenol, or cyanide in isolated liver of fed rats submitted to short-term insulin-induced hypoglycemia (IIH) was investigated. A condition of hyperinsulinemia/hypoglycemia was obtained with an intraperitoneal injection of regular insulin (1.0,U,kg,1). The control group received ip saline. The experiments were carried out 60,min after insulin (IIH group) or saline (COG group) injection. The rats were anesthetized and after laparotomy, blood was collected from the vena cava for glucose and insulin measurements. The liver was then infused with glucagon (1,nM), isoproterenol (2,µM), or cyanide (0.5,mM) during 20,min and a sample of the organ was collected for determination of the activities of glycogen phosphorylase and synthase 5,min after starting and 10,min after stopping the infusions. The infusions of cyanide, glucagons, and isoproterenol did not change the activities of glycogen synthase and glycogen phosphorylase. However, glycogen catabolism was decreased during the infusions of glucagon and isoproterenol in IIH rats, being more intense with isoproterenol (p,<,0.05), than glucagon. It was concluded that short-term IIH promoted changes in the liver responsiveness of glycogen degradation induced by glucagon and isoproterenol without a change in the activities of glycogen phosphorylase and synthase. Copyright © 2008 John Wiley & Sons, Ltd. [source] Identification of mouse heart transcriptomic network sensitive to various heart diseasesBIOTECHNOLOGY JOURNAL, Issue 5 2008Seong-Eui Hong Abstract Exploring biological systems from highly complex datasets is an important task for systems biology. The present study examined co-expression dynamics of mouse heart transcriptome by spectral graph clustering (SGC) to identify a heart transcriptomic network. SGC of microarray data produced 17 classified biological conditions (called condition spectrum, CS) and co-expression patterns by generating bi-clusters. The results showed dynamic co-expression patterns with a modular structure enriched in heart-related CS (CS-1 and -13) containing abundant heart-related microarray data. Consequently, a mouse heart transcriptomic network was constructed by clique analysis from the gene clusters exclusively present in the heart-related CS; 31 cliques were used for constructing the network. The participating genes in the network were closely associated with important cardiac functions (e. g., development, lipid and glycogen metabolisms). Online Mendelian Inheritance in Man (OMIM) database indicates that mutations of the genes in the network induced serious heart diseases. Many of the tested genes in the network showed significantly altered gene expression in an animal model of hypertrophy. The results suggest that the present approach is critical for constructing a heart-related transcriptomic network and for deducing important genes involved in the pathogenesis of various heart diseases. [source] | |||||||||||||