{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T16:04:48Z","timestamp":1780934688293,"version":"3.54.1"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T00:00:00Z","timestamp":1669939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The carotid body chemoreceptors (CBC) play an important role in the adaptive counter\u2010regulatory response to hypoglycaemia by evoking the CBC\u2010mediated sympathetic neuronal system to restore normoglycaemia. <jats:italic>Ex vivo<\/jats:italic> studies have shown varied responses of insulin\u2010induced 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\u2010induced 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\u2010induced 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\u00a0\u00b5g\/kg) were compared before (euglycaemic) and after (hypoglycaemic) intracarotid administration of insulin (12.5\u2013100\u00a0\u00b5U\/dogs) in beagle dogs. Insulin administration increased CSN activity and minute ventilation (<jats:sub>E<\/jats:sub>) with significant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) effects on heart rate and blood pressure. Insulin\u2010mediated effects on CSN and cardiorespiration were sustained and the change in <jats:sub>E<\/jats:sub> was driven by tidal volume only. Insulin significantly (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00.0001) lowered blood glucose level. NaCN\u2010mediated CSN activity and <jats:sub>E<\/jats:sub> were significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) augmented during insulin\u2010induced hypoglycaemia. The augmented <jats:sub>E<\/jats:sub> was primarily driven by respiratory frequency and partially by tidal volume. The cardiovascular reflex response mediated through CBC stimulation was significantly (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.0001) exacerbated during insulin\u2010induced hypoglycaemia. Collectively, these results demonstrate direct effects of insulin and insulin\u2010induced hypoglycaemia on CBC chemosensitivity to potentiate CBC\u2010mediated neuroregulatory pathways to initiate adaptive neuroendocrine and cardiorespiratory counter\u2010regulatory responses to restore normoglycaemia.<\/jats:p>","DOI":"10.1113\/ep090584","type":"journal-article","created":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T19:28:13Z","timestamp":1670009293000},"page":"280-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Acute effects of insulin and insulin\u2010induced hypoglycaemia on carotid body chemoreceptor activity and cardiorespiratory responses in dogs"],"prefix":"10.1113","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4891-9924","authenticated-orcid":false,"given":"Santhosh M.","family":"Baby","sequence":"first","affiliation":[{"name":"Translational Sciences and Treatment 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