{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T19:21:15Z","timestamp":1767986475804,"version":"3.49.0"},"reference-count":49,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"College of Medical and Dental Sciences, University of Birmingham, UK"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2014,10,15]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The carotid body has been proposed to be an acute sensor of hypoglycaemia, although conflicting data exist regarding the ability of hypoglycaemia to stimulate the carotid body directly. The reason for these discrepancies is not known.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In an <jats:italic>in vitro<\/jats:italic>, freshly isolated, intact rat carotid body preparation, chemoafferent function was unaffected and protected against metabolic injury for 30\u00a0min exposure to glucose deprivation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Glycogen granules and glycogen conversion enzymes were identified in type I cells and targeting of glycogenolysis or functional glycogen depletion both caused a more rapid run\u2010down of glycolysis during glucose deprivation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This shows that glycogen maintains carotid body sensory neuronal output in periods of restricted glucose delivery to protect the metabolic integrity of the organ during hypoglycaemia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The preservation of energetic status may account for the variation in the reported capacity of the carotid body to sense physiological glucose concentrations.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1\u00a0\u00b1\u00a01.2\u00a0min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate <jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tjp6289-math-0001.png\" xlink:title=\"urn:x-wiley:00223751:tjp6289:equation:tjp6289-math-0001\"\/> led to proportional decreases in the time to the pre\u2010failure excitation during glucose deprivation which was dependent on a complete run\u2010down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run\u2010down by \u223c33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jphysiol.2014.276105","type":"journal-article","created":{"date-parts":[[2014,7,25]],"date-time":"2014-07-25T10:10:45Z","timestamp":1406283045000},"page":"4493-4506","source":"Crossref","is-referenced-by-count":19,"title":["Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation"],"prefix":"10.1113","volume":"592","author":[{"given":"Andrew P.","family":"Holmes","sequence":"first","affiliation":[{"name":"School of Clinical and Experimental Medicine University of Birmingham  Edgbaston Birmingham B15 2TT UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip 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