{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:08:18Z","timestamp":1794002898773,"version":"4.8.0"},"reference-count":53,"publisher":"American Physiological Society","issue":"4","funder":[{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL131525"],"award-info":[{"award-number":["R01HL131525"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"HHS | NIH | National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL113023"],"award-info":[{"award-number":["R01 HL113023"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.physiology.org"],"crossmark-restriction":true},"short-container-title":["American Journal of Physiology-Lung Cellular and Molecular Physiology"],"published-print":{"date-parts":[[2021,4,1]]},"abstract":"<jats:p>\n                    Obesity increases incidence and severity of asthma but the molecular mechanisms are not completely understood. Hyperinsulinemia potentiates vagally induced bronchoconstriction in obese rats. Since bronchoconstriction results from airway smooth muscle contraction, we tested whether insulin changed agonist-induced airway smooth muscle contraction. Obesity-prone and resistant rats were fed a low-fat diet for 5\u2009wk and treated with insulin (Lantus, 3 units\/rat sc) 16\u2009h before vagally induced bronchoconstriction was measured. Ex vivo, contractile responses to methacholine were measured in isolated rat tracheal rings and human airway smooth muscle strips before and after incubation (0.5\u20132\u2009h) with 100\u2009nM insulin or 13.1\u2009nM insulin like growth factor-1 (IGF-1). M\n                    <jats:sub>2<\/jats:sub>\n                    and M\n                    <jats:sub>3<\/jats:sub>\n                    muscarinic receptor mRNA expression was quantified by qRT-PCR and changes in intracellular calcium were measured in response to methacholine or serotonin in isolated rat tracheal smooth muscle cells treated with 1\u2009\u00b5M insulin. Insulin, administered to animals 16\u2009h prior, potentiated vagally induced bronchoconstriction in both obese-prone and resistant rats. Insulin, not IGF-1, significantly increased methacholine-induced contraction of rat and human isolated airway smooth muscle. In cultured rat tracheal smooth muscle cells, insulin significantly increased M\n                    <jats:sub>2<\/jats:sub>\n                    , not M\n                    <jats:sub>3,<\/jats:sub>\n                    mRNA expression and enhanced methacholine- and serotonin-induced increase in intracellular calcium. Insulin alone did not cause an immediate increase in intracellular calcium. Thus, insulin acutely potentiated agonist-induced increase in intracellular calcium and airway smooth muscle contraction. These findings may explain why obese individuals with hyperinsulinemia are prone to airway hyperreactivity and give insights into future targets for asthma treatment.\n                  <\/jats:p>","DOI":"10.1152\/ajplung.00232.2020","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T08:00:57Z","timestamp":1611734457000},"page":"L545-L556","update-policy":"https:\/\/doi.org\/10.1152\/aps-crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Insulin acutely increases agonist-induced airway smooth muscle contraction in humans and rats"],"prefix":"10.1152","volume":"320","author":[{"given":"Becky J.","family":"Proskocil","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Oregon Health & Science University, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gina N.","family":"Calco","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and 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