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J Physiol Volume 582, Number 2, 859-869, July 15, 2007 DOI: 10.1113/jphysiol.2007.130112
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INTEGRATIVE

The effects of hypo- and hyperglycaemia on the hypoxic ventilatory response in humans

Denham S. Ward1, William A. Voter1 and Suzanne Karan1

1 Departments of Anaesthesiology and Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA

Animal and tissue studies have indicated that the carotid bodies are sensitive to glucose concentrations within the physiological range. This glucose sensitivity may modulate the ventilatory response to hypoxia, with hyperglycaemia suppressing the hypoxic response and hypoglycaemia stimulating it. This study was designed to determine whether hypo- and hyperglycaemia modulate the hypoxic ventilatory response in humans. In 11 normal research participants, glucose levels were clamped at 2.8 and 11.2 mmol l–1 for 30 min. At the start and end of each clamp, blood was drawn for hormone measurement and the isocapnic hypoxic ventilatory response was measured. Because generation of reactive oxygen species may be a common pathway for the interaction between glucose and oxygen levels, the experiments were repeated with and without pretreatment for 1 week with vitamins C and E. Hypoglycaemia caused an increase in the counter-regulatory hormones, a 54% increase in isocapnic ventilation, and a 108% increase in the hypoxic ventilatory response. By contrast, hyperglycaemia resulted in small but significant increases in both ventilation and the hypoxic ventilatory response. Antioxidant vitamin pretreatment altered neither response. In conclusion, the stimulant effect of hypoglycaemia on the hypoxic ventilatory response is consistent with a direct effect on the carotid body, but an indirect effect through the activation of the counter-regulatory response cannot be excluded. The mechanisms behind the mild stimulating effect of hyperglycaemia remain to be elucidated.

(Received 7 February 2007; accepted after revision 30 April 2007; first published online 3 May 2007)
Corresponding author D. S. Ward: Department of Anesthesiology, University of Rochester School of Medicine, 601 Elmwood Avenue, Box 604, Rochester, NY 14642, USA. Email: Denham_Ward{at}URMC.rochester.edu


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Physiological responses to hypoglycaemia - not all 'just in the head'
J. Physiol., July 15, 2007; 582(2): 475 - 476.
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