{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T04:57:05Z","timestamp":1774673825990,"version":"3.50.1"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T00:00:00Z","timestamp":1615939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100010767","name":"Innovative Medicines Initiative","doi-asserted-by":"publisher","award":["777460"],"award-info":[{"award-number":["777460"]}],"id":[{"id":"10.13039\/501100010767","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Diabetologia"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Aims\/hypothesis<\/jats:title>\n                <jats:p>Recurrent hypoglycaemia in people with diabetes leads to progressive suppression of counterregulatory hormonal responses to subsequent hypoglycaemia. Recently it has been proposed that the mechanism underpinning this is a form of adaptive memory referred to as habituation. To test this hypothesis, we use two different durations of cold exposure to examine whether rodents exposed to recurrent hypoglycaemia exhibit two characteristic features of habituation, namely stimulus generalisation and dishabituation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the first study (stimulus generalisation study), hyperinsulinaemic\u2013hypoglycaemic (2.8\u00a0mmol\/l) glucose clamps were performed in non-diabetic rodents exposed to prior moderate-duration cold (4\u00b0C for 3\u00a0h) or control conditions. In the second study (dishabituation study), rodents exposed to prior recurrent hypoglycaemia or saline (154\u00a0mmol\/l NaCl) injections over 4\u00a0weeks underwent a longer-duration cold (4\u00b0C for 4.5\u00a0h) exposure followed 24\u00a0h later by a hyperinsulinaemic\u2013hypoglycaemic (2.8\u00a0mmol\/l) glucose clamp. Output measures were counterregulatory hormone responses during experimental hypoglycaemia.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Moderate-duration cold exposure blunted the adrenaline (epinephrine) response (15,266\u2009\u00b1\u20091920 vs 7981\u2009\u00b1\u20091258\u00a0pmol\/l, Control vs Cold; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) to next day hypoglycaemia in healthy non-diabetic rodents. In contrast, the suppressed adrenaline response (Control 5912\u2009\u00b1\u20091417 vs recurrent hypoglycaemia 1836\u2009\u00b1\u2009736\u00a0pmol\/l; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) that is associated with recurrent hypoglycaemia was restored following longer-duration cold exposure (recurrent hypoglycaemia + Cold 4756\u2009\u00b1\u2009826\u00a0pmol\/l; not significant vs Control).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions\/interpretation<\/jats:title>\n                <jats:p>Non-diabetic rodents exhibit two cardinal features of habituation, namely stimulus generalisation and dishabituation. These findings provide further support for the hypothesis that suppressed counterregulatory responses following exposure to recurrent hypoglycaemia in diabetes result from habituation.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Graphical abstract<\/jats:title>\n                \n              <\/jats:sec>","DOI":"10.1007\/s00125-021-05425-3","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T09:06:18Z","timestamp":1615971978000},"page":"1436-1441","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Cold-induced dishabituation in rodents exposed to recurrent hypoglycaemia"],"prefix":"10.1007","volume":"64","author":[{"given":"Keeran","family":"Vickneson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Blackburn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer R.","family":"Gallagher","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8122-8987","authenticated-orcid":false,"given":"Mark L.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1255-7741","authenticated-orcid":false,"given":"Bastiaan E.","family":"de Galan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-4880","authenticated-orcid":false,"given":"Ulrik","family":"Pedersen-Bjergaard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernard","family":"Thorens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison D.","family":"McNeilly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3957-1981","authenticated-orcid":false,"given":"Rory J.","family":"McCrimmon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,3,17]]},"reference":[{"key":"5425_CR1","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.2337\/diab.41.10.1335","volume":"41","author":"MR Davis","year":"1992","unstructured":"Davis MR, Mellman M, Shamoon H (1992) Further defects in counterregulatory responses induced by recurrent hypoglycemia in IDDM. 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