{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T13:51:35Z","timestamp":1778334695908,"version":"3.51.4"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,6,27]],"date-time":"2016-06-27T00:00:00Z","timestamp":1466985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2016,8]]},"abstract":"<jats:sec><jats:title>New Findings<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item>\n<jats:p><jats:bold>What is the central question of this study?<\/jats:bold><\/jats:p>\n<jats:p>Thyroid dysfunction can have a major impact on pancreatic function. The influence of hyperthyroidism on insulin secretion remains controversial, and the precise mechanism of its effect has not yet been elucidated.<\/jats:p>\n<\/jats:list-item>\n<jats:list-item>\n<jats:p><jats:bold>What is the main finding and its importance?<\/jats:bold><\/jats:p>\n<jats:p>The results of this study demonstrate that hyperthyroidism leads to impaired insulin secretion. It appears that the defect in insulin secretion in the hyperthyroid state probably reflects a summation of different alterations, including decreased sensitivity of ATP\u2010sensitive K<jats:sup>+<\/jats:sup> and L\u2010type Ca<jats:sup>2+<\/jats:sup> channels of the \u03b2\u2010cells and reduced \u03b2\u2010cell mass.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>To clarify the mechanism underlying the effect of thyroid hormone excess on pancreatic insulin secretion and abnormal glucose tolerance induced by hyperthyroidism, we investigated the effect of hyperthyroidism on the pancreatic \u03b2\u2010cell mass and two key components of the insulin secretory pathway, ATP\u2010sensitive K<jats:sup>+<\/jats:sup> (K<jats:sub>ATP<\/jats:sub>) and L\u2010type Ca<jats:sup>2+<\/jats:sup> channels. In control and levothyroxine\u2010treated hyperthyroid rats, an intraperitoneal glucose tolerance test was performed, and the insulin secretion and content of the isolated islets were assayed. In order to determine the effect of hyperthyroidism on K<jats:sub>ATP<\/jats:sub> and L\u2010type Ca<jats:sup>2+<\/jats:sup> channels, isolated islets were exposed to specific pharmacological agents, including glibenclamide (K<jats:sub>ATP<\/jats:sub> channel blocker), diazoxide (K<jats:sub>ATP<\/jats:sub> channel opener) and nifedipine (L\u2010type Ca<jats:sup>2+<\/jats:sup> channel blocker). Histomorphometric changes and histochemistry of the islet in both groups were compared. Our data indicated that plasma glucose and insulin concentrations during the intraperitoneal glucose tolerance test in the hyperthyroid group were, respectively, higher and lower than in the control group. Insulin secretion and content of the hyperthyroid islets were reduced. The response of hyperthyroid islets to glibenclamide, diazoxide and nifedipine and the percentage change in insulin secretion were lower than those of the control islets. Despite the increase in weight and total volume of the pancreas, the volume of the islets and the total number of insulin\u2010positive cells in hyperthyroid rats were reduced. Our data indicated that reduced insulin secretion in the hyperthyroid group might arise from reduced \u03b2\u2010cell mass and an abnormality in some parts of the insulin secretory pathway, including K<jats:sub>ATP<\/jats:sub> and L\u2010type Ca<jats:sup>2+<\/jats:sup> channel function.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep085627","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T14:42:34Z","timestamp":1460299354000},"page":"1114-1127","source":"Crossref","is-referenced-by-count":22,"title":["Impaired glucose\u2010stimulated insulin secretion and reduced \u03b2\u2010cell mass in pancreatic islets of hyperthyroid rats"],"prefix":"10.1113","volume":"101","author":[{"given":"Narges","family":"Karbalaei","sequence":"first","affiliation":[{"name":"Histomorphometry and Stereology Research Center Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Department of Physiology, Faculty of Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Noorafshan","sequence":"additional","affiliation":[{"name":"Histomorphometry and Stereology Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebrahim","family":"Hoshmandi","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,6,27]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0849"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/rp.56.1.47"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.4158\/EP.12.2.121"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310385140"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1177\/1474651410371321"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.4061\/2011\/152850"},{"key":"e_1_2_5_8_1","first-page":"181","article-title":"Effect of thyroid hormone levels upon pancreatic islet function","volume":"35","author":"Cortizo AM","year":"1985","journal-title":"Acta Physiol Pharmacol Latinoam"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i45.17196"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/105072502760143809"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1985.248.5.E593"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2001-18584"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0026-0495(97)90294-8"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.55.1.7"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104184"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01121.x"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024-3205(02)01791-5"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1988.tb05320.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90700.2008"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(90)90354-N"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-002-0842-5"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365513.2012.743164"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2013.073825"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012479199"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.1.06110"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-99-1-125"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-103-5-1546"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)44841-1"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1159-8"},{"key":"e_1_2_5_30_1","first-page":"1044","article-title":"Pancreatic and islet development and function: the role of thyroid hormone","volume":"2","author":"Mastracci TL","year":"2014","journal-title":"J Endocrinol Diabetes Obes"},{"key":"e_1_2_5_31_1","first-page":"16","article-title":"Comparison between stereology methods for cell volume assessment: exemplified by estimation of neuronal nuclear volume in cirrhotic rats","volume":"12","author":"M\u00e9ndez M","year":"2007","journal-title":"Revista Electr\u00f3nica de Metodolog\u00eda Aplicada"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.2337\/diab.41.10.1221","article-title":"Electrophysiology of stimulus\u2010secretion coupling in human \u03b2\u2010cells","volume":"41","author":"Misler S","year":"1992","journal-title":"Diabetes"},{"key":"e_1_2_5_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/0531-5565(90)90006-N"},{"key":"e_1_2_5_34_1","first-page":"427","article-title":"A simple stereological method for estimating the number and the volume of the pancreatic beta cells","volume":"13","author":"Noorafshan A","year":"2012","journal-title":"JOP"},{"key":"e_1_2_5_35_1","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.34.339"},{"key":"e_1_2_5_36_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114961"},{"key":"e_1_2_5_37_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2007-0023"},{"key":"e_1_2_5_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01396-09"},{"key":"e_1_2_5_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R400019200"},{"key":"e_1_2_5_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-4-1-63"},{"issue":"5","key":"e_1_2_5_41_1","first-page":"S133","article-title":"Hyperthyroidism induces glucose intolerance by lowering both insulin secretion and peripheral insulin sensitivity","volume":"89","author":"Roubsanthisuk W","year":"2006","journal-title":"J Med Assoc Thai"},{"key":"e_1_2_5_42_1","doi-asserted-by":"publisher","DOI":"10.3126\/ajms.v6i6.12603"},{"key":"e_1_2_5_43_1","first-page":"57","article-title":"A simple method for volumetry of organs in quantitative stereology","volume":"26","author":"Scherle W","year":"1970","journal-title":"Mikroskopie"},{"key":"e_1_2_5_44_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389450116666150204113928"},{"key":"e_1_2_5_45_1","first-page":"96","article-title":"Insulin secretion, adipocyte insulin binding and insulin sensitivity in thyrotoxicosis","volume":"109","author":"Taylor R","year":"1985","journal-title":"Acta Endocrinol (Copenh)"},{"key":"e_1_2_5_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2007.03.001"},{"key":"e_1_2_5_47_1","first-page":"49","article-title":"Thyroid hormone increased L\u2010type calcium channel mRNA expression and L\u2010type calcium current of myocytes in rabbits","volume":"22","author":"Yu Z","year":"2012","journal-title":"Biomed Mater Eng"},{"key":"e_1_2_5_48_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2003-40463"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FEP085627","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP085627","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T14:37:35Z","timestamp":1695998255000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP085627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,6,27]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2016,8]]}},"alternative-id":["10.1113\/EP085627"],"URL":"https:\/\/doi.org\/10.1113\/ep085627","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,6,27]]}}}