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The Biochemical Journal Feb 2012Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been... (Review)
Review
Glycogen is a branched polymer of glucose that acts as a store of energy in times of nutritional sufficiency for utilization in times of need. Its metabolism has been the subject of extensive investigation and much is known about its regulation by hormones such as insulin, glucagon and adrenaline (epinephrine). There has been debate over the relative importance of allosteric compared with covalent control of the key biosynthetic enzyme, glycogen synthase, as well as the relative importance of glucose entry into cells compared with glycogen synthase regulation in determining glycogen accumulation. Significant new developments in eukaryotic glycogen metabolism over the last decade or so include: (i) three-dimensional structures of the biosynthetic enzymes glycogenin and glycogen synthase, with associated implications for mechanism and control; (ii) analyses of several genetically engineered mice with altered glycogen metabolism that shed light on the mechanism of control; (iii) greater appreciation of the spatial aspects of glycogen metabolism, including more focus on the lysosomal degradation of glycogen; and (iv) glycogen phosphorylation and advances in the study of Lafora disease, which is emerging as a glycogen storage disease.
Topics: Amino Acid Sequence; Animals; Biology; Carbohydrate Metabolism; Concept Formation; Gluconeogenesis; Glycogen; Glycogenolysis; Humans; Metabolic Networks and Pathways; Mice; Models, Biological; Models, Molecular; Molecular Sequence Data; Sequence Homology, Amino Acid
PubMed: 22248338
DOI: 10.1042/BJ20111416 -
Advances in Experimental Medicine and... 2015Glucocorticoids are steroid hormones that regulate multiple aspects of glucose homeostasis. Glucocorticoids promote gluconeogenesis in liver, whereas in skeletal muscle... (Review)
Review
Glucocorticoids are steroid hormones that regulate multiple aspects of glucose homeostasis. Glucocorticoids promote gluconeogenesis in liver, whereas in skeletal muscle and white adipose tissue they decrease glucose uptake and utilization by antagonizing insulin response. Therefore, excess glucocorticoid exposure causes hyperglycemia and insulin resistance. Glucocorticoids also regulate glycogen metabolism. In liver, glucocorticoids increase glycogen storage, whereas in skeletal muscle they play a permissive role for catecholamine-induced glycogenolysis and/or inhibit insulin-stimulated glycogen synthesis. Moreover, glucocorticoids modulate the function of pancreatic α and β cells to regulate the secretion of glucagon and insulin, two hormones that play a pivotal role in the regulation of blood glucose levels. Overall, the major glucocorticoid effect on glucose homeostasis is to preserve plasma glucose for brain during stress, as transiently raising blood glucose is important to promote maximal brain function. In this chapter we will discuss the current understanding of the mechanisms underlying different aspects of glucocorticoid-regulated mammalian glucose homeostasis.
Topics: Animals; Glucocorticoids; Gluconeogenesis; Glucose; Glycogen; Homeostasis; Humans
PubMed: 26215992
DOI: 10.1007/978-1-4939-2895-8_5 -
Nutrients Jun 2020Rowing is a high-intensity sport requiring a high level of aerobic and anaerobic capacity. Although good nutrition is essential for successful performance in a rowing... (Meta-Analysis)
Meta-Analysis
Rowing is a high-intensity sport requiring a high level of aerobic and anaerobic capacity. Although good nutrition is essential for successful performance in a rowing competition, its significance is not sufficiently established. This review aimed to provide nutritional strategies to optimize performance and recovery in rowing athletes based on a literature review. Following the guidelines given in the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA), we performed web searches using online databases (Pubmed, Web of Science, Wiley Online Library, ACS Publications, and SciFinder). Typically, a rowing competition involves a 6-8-min high-intensity exercise on a 2000-m course. The energy required for the exercise is supplied by muscle-stored glycogens, which are derived from carbohydrates. Therefore, rowing athletes can plan their carbohydrate consumption based on the intensity, duration, and type of training they undergo. For effective and safe performance enhancement, rowing athletes can take supplements such as β-alanine, caffeine, β-hydroxy-β-methylbutyric acid (HMB), and beetroot juice (nitrate). An athlete may consume carbohydrate-rich foods or use a carbohydrate mouth rinse. Recovery nutrition is also very important to minimize the risk of injury or unexplained underperformance syndrome (UUPS) from overuse. It must take into account refueling (carbohydrate), rehydration (fluid), and repair (protein). As lightweight rowing athletes often attempt acute weight loss by limiting food and fluid intake to qualify for a competition, they require personalized nutritional strategies and plans based on factors such as their goals and environment. Training and competition performance can be maximized by including nutritional strategies in training plans.
Topics: Athletes; Athletic Performance; Caffeine; Dietary Carbohydrates; Dietary Supplements; Energy Metabolism; Female; Fluid Therapy; Glycogen; Humans; Male; Muscle, Skeletal; Nitrates; Nutritional Physiological Phenomena; Nutritional Requirements; Physical Conditioning, Human; Water Sports; beta-Alanine
PubMed: 32516908
DOI: 10.3390/nu12061685 -
International Journal of Molecular... Mar 2023The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the... (Review)
Review
The liver is a major store of glycogen and is essential in maintaining systemic glucose homeostasis. In healthy individuals, glycogen synthesis and breakdown in the liver are tightly regulated. Abnormal glycogen metabolism results in prominent pathological changes in the liver, often manifesting as hepatic glycogenosis or glycogen inclusions. This can occur in genetic glycogen storage disease or acquired conditions with insulin dysregulation such as diabetes mellitus and non-alcoholic fatty liver disease or medication effects. Some primary hepatic tumors such as clear cell hepatocellular carcinoma also demonstrate excessive glycogen accumulation. This review provides an overview of the pathological manifestations and molecular mechanisms of liver diseases associated with abnormal glycogen accumulation.
Topics: Humans; Glycogen; Liver; Carcinoma, Hepatocellular; Liver Neoplasms; Glycogen Storage Disease
PubMed: 37047105
DOI: 10.3390/ijms24076133 -
Biomolecules Jul 2020For complex carbohydrates, such as glycogen and starch, various analytical methods and techniques exist allowing the detailed characterization of these storage... (Review)
Review
For complex carbohydrates, such as glycogen and starch, various analytical methods and techniques exist allowing the detailed characterization of these storage carbohydrates. In this article, we give a brief overview of the most frequently used methods, techniques, and results. Furthermore, we give insights in the isolation, purification, and fragmentation of both starch and glycogen. An overview of the different structural levels of the glucans is given and the corresponding analytical techniques are discussed. Moreover, future perspectives of the analytical needs and the challenges of the currently developing scientific questions are included.
Topics: Chromatography, Gel; Glycogen; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Starch
PubMed: 32660096
DOI: 10.3390/biom10071020 -
The Journal of Biological Chemistry Jul 2022Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially... (Review)
Review
Autophagy is an essential cellular process involving degradation of superfluous or defective macromolecules and organelles as a form of homeostatic recycling. Initially proposed to be a "bulk" degradation pathway, a more nuanced appreciation of selective autophagy pathways has developed in the literature in recent years. As a glycogen-selective autophagy process, "glycophagy" is emerging as a key metabolic route of transport and delivery of glycolytic fuel substrate. Study of glycophagy is at an early stage. Enhanced understanding of this major noncanonical pathway of glycogen flux will provide important opportunities for new insights into cellular energy metabolism. In addition, glycogen metabolic mishandling is centrally involved in the pathophysiology of several metabolic diseases in a wide range of tissues, including the liver, skeletal muscle, cardiac muscle, and brain. Thus, advances in this exciting new field are of broad multidisciplinary interest relevant to many cell types and metabolic states. Here, we review the current evidence of glycophagy involvement in homeostatic cellular metabolic processes and of molecular mediators participating in glycophagy flux. We integrate information from a variety of settings including cell lines, primary cell culture systems, ex vivo tissue preparations, genetic disease models, and clinical glycogen disease states.
Topics: Autophagy; Glycogen; Glycogenolysis; Macroautophagy
PubMed: 35654138
DOI: 10.1016/j.jbc.2022.102093 -
Advances in Neurobiology 2019Brain glycogen is stored mainly in astrocytes, although neurons also have an active glycogen metabolism. Glycogen has gained relevance as a key player in brain function.... (Review)
Review
Brain glycogen is stored mainly in astrocytes, although neurons also have an active glycogen metabolism. Glycogen has gained relevance as a key player in brain function. In this regard, genetically modified animals have allowed researchers to unravel new roles of this polysaccharide in the brain. Remarkably, mice in which glycogen synthase is abolished in the brain, and thus devoid of brain glycogen, are viable, thereby indicating that the polysaccharide in this organ is not a requirement for survival. While there was growing evidence supporting a role of glycogen in learning and memory, these animals have now confirmed that glycogen participates in these two processes.The association of epilepsy with brain glycogen has also attracted attention. Analysis of genetically modified mice indicates that the relation between brain glycogen and epilepsy is complex. While the formation of glycogen aggregates clearly underlies epilepsy, as in Lafora Disease (LD), the absence of glycogen also favors the occurrence of seizures.LD is a rare genetic condition that affects children. It is characterized by epileptic seizures and neurodegeneration, and it develops rapidly until finally causing death. Research into this disease has unveiled new aspects of glycogen metabolism. Animal models of LD accumulate polyglucosan bodies formed by aberrant glycogen aggregates, called Lafora bodies (LBs). The abolition of glycogen synthase (GS) prevents the formation of LBs and the development of LD, thereby indicating that glycogen accumulation underlies this disease and the associated symptoms, and thus establishing a clear relation between the accumulation of glycogen aggregates and the incidence of seizures.Although it was initially accepted that LBs were essentially neuronal, it is now evident that astrocytes also accumulate polyglucosan aggregates in LD. However, the appearance and composition of these deposits differs from that observed in neurons. Of note, the astrocytic aggregates in LD models show remarkable similarities with corpora amylacea (CA), a type of polyglucosan aggregate observed in the brains of aged mice and humans. The abolition of GS in mice also impedes the formation of CA with age and at the same time prevents the formation of a number of protein aggregates associated with aging. Therefore CA may play a role in age-related neurological decline.
Topics: Aging; Animals; Astrocytes; Glycogen; Glycogen Synthase; Humans; Lafora Disease; Neurons
PubMed: 31667813
DOI: 10.1007/978-3-030-27480-1_10 -
Cell Metabolism Feb 2021Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use C-tracing in mice to quantify...
Glycolysis plays a central role in organismal metabolism, but its quantitative inputs across mammalian tissues remain unclear. Here we use C-tracing in mice to quantify glycolytic intermediate sources: circulating glucose, intra-tissue glycogen, and circulating gluconeogenic precursors. Circulating glucose is the main source of circulating lactate, the primary end product of tissue glycolysis. Yet circulating glucose highly labels glycolytic intermediates in only a few tissues: blood, spleen, diaphragm, and soleus muscle. Most glycolytic intermediates in the bulk of body tissue, including liver and quadriceps muscle, come instead from glycogen. Gluconeogenesis contributes less but also broadly to glycolytic intermediates, and its flux persists with physiologic feeding (but not hyperinsulinemic clamp). Instead of suppressing gluconeogenesis, feeding activates oxidation of circulating glucose and lactate to maintain glucose homeostasis. Thus, the bulk of the body slowly breaks down internally stored glycogen while select tissues rapidly catabolize circulating glucose to lactate for oxidation throughout the body.
Topics: Animals; Blood Glucose; Carbon Isotopes; Diaphragm; Gluconeogenesis; Glycogen; Glycolysis; Male; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Spleen
PubMed: 33472024
DOI: 10.1016/j.cmet.2020.12.020 -
International Journal of Molecular... Jan 2023Glycogen, the branched polymer of glucose is found mainly in the liver and muscle in mammals. Along with several other proteins, glycogen forms separate cellular... (Review)
Review
Glycogen, the branched polymer of glucose is found mainly in the liver and muscle in mammals. Along with several other proteins, glycogen forms separate cellular organelles, and particles in cells. Glycogen particles in the liver have a special metabolic and also regulatory connection to the intracellular endomembrane system, particularly the endoplasmic reticulum. This connection is part of the organelle homeostasis in hepatocytes and forms a "glycogenoreticular system". The actual size of hepatic glycogen stores and the rate of glycogenolysis determines several essential liver-specific metabolic processes, such as glucose secretion for the maintenance of blood glucose levels or the glucuronidation of certain vital endo-, and xenobiotics, and are also related to liver antioxidant defense. In starvation, and in certain physiological and pathological states, where glycogen stores are depleted, functions of the glycogenoreticular system are altered. The starvation-induced depletion of hepatic glycogen content changes the biotransformation of various endo- and xenobiotics. This can be observed especially in acute DILI (drug-induced liver injury) due to paracetamol overdose, which is the most common cause of acute liver failure in the West.
Topics: Animals; Glycogen; Liver Glycogen; Xenobiotics; Liver; Glucose; Endoplasmic Reticulum; Mammals
PubMed: 36674588
DOI: 10.3390/ijms24021074 -
The Journal of Physiology Sep 2013Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on... (Review)
Review
Studies performed at the beginning of the last century revealed the importance of carbohydrate as a fuel during exercise, and the importance of muscle glycogen on performance has subsequently been confirmed in numerous studies. However, the link between glycogen depletion and impaired muscle function during fatigue is not well understood and a direct cause-and-effect relationship between glycogen and muscle function remains to be established. The use of electron microscopy has revealed that glycogen is not homogeneously distributed in skeletal muscle fibres, but rather localized in distinct pools. Furthermore, each glycogen granule has its own metabolic machinery with glycolytic enzymes and regulating proteins. One pool of such glycogenolytic complexes is localized within the myofibrils in close contact with key proteins involved in the excitation-contraction coupling and Ca2+ release from the sarcoplasmic reticulum (SR). We and others have provided experimental evidence in favour of a direct role of decreased glycogen, localized within the myofibrils, for the reduction in SR Ca2+ release during fatigue. This is consistent with compartmentalized energy turnover and distinctly localized glycogen pools being of key importance for SR Ca2+ release and thereby affecting muscle contractility and fatigability.
Topics: Animals; Calcium; Glycogen; Humans; Muscle Fatigue; Muscle, Skeletal
PubMed: 23652590
DOI: 10.1113/jphysiol.2013.251629