Purinergic receptors expressed in human skeletal muscle fibres
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Purinergic receptors are present in most tissues and thought to be involved in various signalling pathways, including neural signalling, cell metabolism and local regulation of the microcirculation in skeletal muscles. The present study aims to determine the distribution and intracellular content of purinergic receptors in skeletal muscle fibres in patients with type 2 diabetes and age-matched controls. Muscle biopsies from vastus lateralis were obtained from six type 2 diabetic patients and seven age-matched controls. Purinergic receptors were analysed using light and confocal microscopy in immunolabelled transverse sections of muscle biopsies. The receptors P2Y4, P2Y11 and likely P2X1 were present intracellularly or in the plasma membrane of muscle fibres and were thus selected for further detailed morphological analysis. P2X1 receptors were expressed in intracellular vesicles and sarcolemma. P2Y4 receptors were present in sarcolemma. P2Y11 receptors were abundantly and diffusely expressed intracellularly and were more explicitly expressed in type I than in type II fibres, whereas P2X1 and P2Y4 showed no fibre-type specificity. Both diabetic patients and healthy controls showed similar distribution of receptors. The current study demonstrates that purinergic receptors are located intracellularly in human skeletal muscle fibres. The similar cellular localization of receptors in healthy and diabetic subjects suggests that diabetes is not associated with an altered distribution of purinergic receptors in skeletal muscle fibres. We speculate that the intracellular localization of purinergic receptors may reflect a role in regulation of muscle metabolism; further studies are nevertheless needed to determine the function of the purinergic system in skeletal muscle cells.
KeywordsP2Y receptors P2X receptors Type 2 diabetes Muscle metabolism
We thank Nethe Kristensen for technical support and Professor Ylva Hellsten and Professor Bengt Saltin (The Copenhagen Muscle Research Centre) for guidance and assistance. Novo Nordisk A/S financially supported the study.
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