Experimental Physiology (Feb 2023)

Acute effects of insulin and insulin‐induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs

  • Santhosh M. Baby,
  • Faisal Zaidi,
  • Gerald E. Hunsberger,
  • David Sokal,
  • Isha Gupta,
  • Silvia V. Conde,
  • Daniel Chew,
  • Kristen Rall,
  • Robert W. Coatney

DOI
https://doi.org/10.1113/EP090584
Journal volume & issue
Vol. 108, no. 2
pp. 280 – 295

Abstract

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Abstract The carotid body chemoreceptors (CBC) play an important role in the adaptive counter‐regulatory response to hypoglycaemia by evoking the CBC‐mediated sympathetic neuronal system to restore normoglycaemia. Ex vivo studies have shown varied responses of insulin‐induced hypoglycaemia on CBC function, and several in vivo studies have indirectly established the role of CBCs in restoring normoglycaemia in both animals and humans. However, a direct effect of insulin and/or insulin‐induced hypoglycaemia on CBC activity is not established in animal models. Therefore, the aim of this study was to evaluate in vivo effects of insulin and insulin‐induced hypoglycaemia on CBC activity and cardiorespiration in a preclinical large animal model. The carotid sinus nerve (CSN) activity and cardiorespiratory responses to sodium cyanide (NaCN; 25 µg/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5–100 µU/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation (V̇E) with significant (P < 0.0001) effects on heart rate and blood pressure. Insulin‐mediated effects on CSN and cardiorespiration were sustained and the change in V̇E was driven by tidal volume only. Insulin significantly (P < 0.0001) lowered blood glucose level. NaCN‐mediated CSN activity and V̇E were significantly (P < 0.0001) augmented during insulin‐induced hypoglycaemia. The augmented V̇E was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (P < 0.0001) exacerbated during insulin‐induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin‐induced hypoglycaemia on CBC chemosensitivity to potentiate CBC‐mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter‐regulatory responses to restore normoglycaemia.

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