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      The role of the microcirculation in muscle function and plasticity

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          Abstract

          It is widely acknowledged that maintenance of muscle, size, strength and endurance is necessary for quality of life and the role that skeletal muscle microcirculation plays in muscle health is becoming increasingly clear. Here we discuss the role that skeletal muscle microcirculation plays in muscle function and plasticity. Besides the density of the capillary network, also the distribution of capillaries is crucial for adequate muscle oxygenation. While capillaries are important for oxygen delivery, the capillary supply to a fibre is related to fibre size rather than oxidative capacity. This link between fibre size and capillary supply is also reflected by the similar time course of hypertrophy and angiogenesis, and the cross-talk between capillaries and satellite cells. A dense vascular network may in fact be more important for a swift repair of muscle damage than the abundance of satellite cells and a lower capillary density may also attenuate the hypertrophic response. Capillary rarefaction does not only occur during ageing, but also during conditions as chronic heart failure, where endothelial apoptosis has been reported to precede muscle atrophy. It has been suggested that capillary rarefaction precedes sarcopenia. If so, stimulation of angiogenesis by for instance endurance training before a hypertrophic stimulus may enhance the hypertrophic response. The microcirculation may thus well be a little-explored target to improve muscle function and the success of rehabilitation programmes during ageing and chronic diseases.

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          The number and distribution of capillaries in muscles with calculations of the oxygen pressure head necessary for supplying the tissue.

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            Amino Acid Restriction Triggers Angiogenesis via GCN2/ATF4 Regulation of VEGF and H 2 S Production

            Angiogenesis, the formation of new blood vessels by endothelial cells (EC), is an adaptive response to oxygen/nutrient deprivation orchestrated by vascular endothelial growth factor (VEGF) upon ischemia or exercise. Hypoxia is the best-understood trigger of VEGF expression via the transcription factor HIF1α. Nutrient deprivation is inseparable from hypoxia during ischemia, yet its role in angiogenesis is poorly characterized. Here, we identified sulfur amino acid restriction as a proangiogenic trigger, promoting increased VEGF expression, migration and sprouting in EC in vitro, and increased capillary density in mouse skeletal muscle in vivo, via the GCN2/ATF4 amino acid starvation response pathway independent of hypoxia or HIF1α. We also identified a requirement for cystathionine-γ-lyase in VEGF-dependent angiogenesis via increased hydrogen sulfide (H 2 S) production. H 2 S mediated its proangiogenic effects in part by inhibiting mitochondrial electron transport and oxidative phosphorylation, resulting in increased glucose uptake and glycolytic ATP production. Restricting dietary sulfur can trigger angiogenesis and improve vascular health
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              The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise

              Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g). Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycemic clamp, 70–90% of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake ( V o 2 max ⁡ ) and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new “fight or flight” events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes.
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                Author and article information

                Contributors
                +44.161.247.5686 , h.degens@mmu.ac.uk
                Journal
                J Muscle Res Cell Motil
                J. Muscle Res. Cell. Motil
                Journal of Muscle Research and Cell Motility
                Springer International Publishing (Cham )
                0142-4319
                1573-2657
                5 June 2019
                5 June 2019
                2019
                : 40
                : 2
                : 127-140
                Affiliations
                [1 ]ISNI 0000 0001 0790 5329, GRID grid.25627.34, Research Centre for Musculoskeletal Science & Sports Medicine, School of Healthcare Science, , Manchester Metropolitan University, ; John Dalton Building; Chester Street, Manchester, M1 5GD UK
                [2 ]ISNI 0000 0000 9487 602X, GRID grid.419313.d, Lithuanian Sports University, ; Kaunas, Lithuania
                [3 ]ISNI 0000 0001 0738 9977, GRID grid.10414.30, University of Medicine and Pharmacy of Targu Mures, ; Targu Mures, Romania
                Author information
                http://orcid.org/0000-0003-2769-7816
                Article
                9520
                10.1007/s10974-019-09520-2
                6726668
                31165949
                e20289bd-21c9-4d98-bb01-b2c965761cd8
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 25 April 2019
                : 31 May 2019
                Categories
                Article
                Custom metadata
                © Springer Nature Switzerland AG 2019

                Molecular biology
                capillary,muscle,hypertrophy,oxidative capacity,angiogenesis,microcirculation
                Molecular biology
                capillary, muscle, hypertrophy, oxidative capacity, angiogenesis, microcirculation

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