title: Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.
abstract: 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 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down 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-down by ∼33 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.
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors: Andrew P
authors: AP
authors: Holmes
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors: Philip J
authors: PJ
authors: Turner
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors: Paul
authors: P
authors: Carter
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors: Wendy
authors: W
authors: Leadbeater
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors: Clare J
authors: CJ
authors: Ray
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
authors: David
authors: D
authors: Hauton
authors: Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, OX1 3PT, UK.
authors: Keith J
authors: KJ
authors: Buckler
authors: School of Clinical and Experimental Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK p.kumar@bham.ac.uk.
authors: Prem
authors: P
authors: Kumar
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000378:metabolism / Q000648:ultrastructure; D005947:Glucose / Q000172:deficiency* / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D050261:Glycogenolysis; D006019:Glycolysis; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D006003:Glycogen; D005947:Glucose