{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:29:51Z","timestamp":1784554191970,"version":"3.55.0"},"reference-count":51,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T00:00:00Z","timestamp":1621900800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2017\/04580\u20102"],"award-info":[{"award-number":["2017\/04580\u20102"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2018\/1699\u20100"],"award-info":[{"award-number":["2018\/1699\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2019\/26062\u20109"],"award-info":[{"award-number":["2019\/26062\u20109"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2014\/50867\u20103"],"award-info":[{"award-number":["2014\/50867\u20103"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Experimental Physiology"],"published-print":{"date-parts":[[2021,7]]},"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>Type 1 diabetes mellitus (T1D) leads to hyperglycaemia owing to pancreatic \u03b2\u2010cell destruction by the immune system. Physical exercise has been shown to have potentially beneficial protective roles against cytokine\u2010induced pancreatic \u03b2\u2010cell death, but its benefits are yet to be proved and should be understood better, especially in the islet environment.<\/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>Physical exercise protects against \u03b2\u2010cell loss in a well\u2010described animal model for T1D, induced by multiple low doses of streptozotocin. This seems to be related to reduced cytokine\u2010induced \u03b2\u2010cell death and increased islet cell proliferation. Contributions of islet neogenesis and\/or transdifferentiation of pancreatic non\u2010\u03b2\u2010cells into \u03b2\u2010cells cannot be excluded.<\/jats:p>\n<\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Physical exercise has beneficial effects on pancreatic \u03b2\u2010cell function and survival in a pro\u2010inflammatory environment. Although these effects have been linked to decreased islet inflammation and modulation of pro\u2010apoptotic pathways, little is known about the islet microenvironment. Our aim was to evaluate the effects of physical exercise in islet histomorphology in a mouse model of type\u00a01 diabetes mellitus induced by multiple low doses of streptozotocin. As expected, induction of type\u00a01 diabetes mellitus led to \u03b2\u2010cell loss and, consequently, decreased islet area. Interestingly, although the decrease in islet area was not prevented by physical exercise, this was not the case for the decrease in \u03b2\u2010cell mass. This was probably related to induction of \u03b2\u2010cell regeneration, because we observed increased proliferation and regeneration markers, such as Ki67 and Pcna, in islets of trained mice. These were found in the central and peripheral regions of the islets. An increase in the percentage of \u03b1\u2010 and \u03b4\u2010cells in these conditions, combined with an increase in proliferation and Pax4 labelling in peripheral regions, suggest that \u03b2\u2010cell regeneration might also occur by transdifferentiation. This agrees with the presence of cells double stained for insulin and glucagon only in islets of diabetic trained mice. In addition, this group had more extra\u2010islet insulin\u2010positive cells and islets associated with ducts than diabetic mice. Physical exercise also decreased nuclear factor\u2010\u03baB activation in islet cells of diabetic trained compared with diabetic untrained mice, indicating a decrease in pro\u2010inflammatory cytokine\u2010induced \u03b2\u2010cell death. Taken together, these findings indicate that preservation of \u03b2\u2010cell mass induced by physical exercise involves an increase in \u03b2\u2010cell replication and decrease in \u03b2\u2010cell death, together with islet neogenesis and islet cell transdifferentiation.<\/jats:p><\/jats:sec>","DOI":"10.1113\/ep088872","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T07:25:49Z","timestamp":1619681149000},"page":"1482-1497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Beneficial effects of physical exercise for \u03b2\u2010cell maintenance in a type 1 diabetes mellitus animal model"],"prefix":"10.1113","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7301-126X","authenticated-orcid":false,"given":"Catharina de Barros Pimentel","family":"Villa\u00e7a","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina Cavalcante","family":"de Paula","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3137-6911","authenticated-orcid":false,"given":"Caroline Cruz","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1565-1618","authenticated-orcid":false,"given":"Eloisa Aparecida","family":"Vilas\u2010Boas","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8667-8140","authenticated-orcid":false,"given":"Junia Carolina","family":"dos Santos\u2010Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Faculty of Medical Sciences State University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9rgio Ferreira","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4273-1608","authenticated-orcid":false,"given":"Fernando","family":"Abdulkader","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra Mara","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Structural and Functional Biology Institute of Biology State University of Campinas  Campinas Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9551-2839","authenticated-orcid":false,"given":"Fernanda","family":"Ortis","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology Institute of Biomedical Sciences (ICB) University of S\u00e3o Paulo (USP)  S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201017204\u20105"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2012.9.407"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415583535"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510790103"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13633"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010010\u20101851\u20104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2010.7.124"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.269003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2010.07.007"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.203.145"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463\u20101326.2011.01441.x"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12164"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature02520"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201704044"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2009.21"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508166103"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22098"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748\u20101716.2007.01783.x"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.2337\/db10\u20101102"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/481427"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00569.2007"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700687"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2012.01911.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.12.6212"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64095"},{"key":"e_1_2_9_27_1","first-page":"238","article-title":"Diabetes induced by multiple low doses of STZ can be spontaneously recovered in adult mice","volume":"34","author":"Li R.\u2010J.","year":"2013","journal-title":"Dong Wu Xue Yan Jiu = Zoological Research"},{"key":"e_1_2_9_28_1","first-page":"470","article-title":"Streptozotocin\u2010induced pancreatic insulitis in mice. Morphologic and physiologic studies","volume":"38","author":"Like A. A.","year":"1978","journal-title":"Laboratory Investigation"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00653"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1530\/jme\u201016\u20100183"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/dme.13439"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125\u2010014\u20103412\u20108"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2015.07.014"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)10969896(199602)178"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005\u20100268"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1530\/ec\u201017\u20100347"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700710R"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14\u2010264820"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90931.2008"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.3109\/08916939509001931"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc09\u20100374"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2019"},{"key":"e_1_2_9_44_1","first-page":"559","article-title":"Intermediate filaments as differentiation markers of normal pancreas and pancreas cancer","volume":"140","author":"Sch\u00fcssler M. H.","year":"1992","journal-title":"The American Journal of Pathology"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00257788"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2015.10.002"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1530\/ec\u201018\u20100505"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.07.090"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08894"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12721"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066214"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2009.03.114"}],"container-title":["Experimental Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP088872","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1113\/EP088872","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/EP088872","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T14:16:46Z","timestamp":1692886606000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/EP088872"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,25]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1113\/EP088872"],"URL":"https:\/\/doi.org\/10.1113\/ep088872","archive":["Portico"],"relation":{},"ISSN":["0958-0670","1469-445X"],"issn-type":[{"value":"0958-0670","type":"print"},{"value":"1469-445X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,25]]},"assertion":[{"value":"2020-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}