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To determine the effect of long term diabetes on bone we used adult and aging <jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup> mice that developed T1DM around 3\u20134 weeks after birth. Both \n<jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup> and wild\u2010type (WT) mice were analyzed at 4, 6, and 12 months to assess bone parameters such as femur length, growth plate thickness and number of mature and preapoptotic chondrocytes. In addition, bone microarchitecture of the cortical and trabecular regions was measured by microcomputed tomography and gene expression of \n<jats:italic>Adamst\u20105, Col2, Igf1, Runx2, Acp5<\/jats:italic>, and \n<jats:italic>Oc<\/jats:italic> was quantified by quantitative real\u2010time polymerase chain reaction. \n<jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup> mice showed a decreased longitudinal growth of the femur that was related to decreased growth plate thickness, lower number of chondrocytes and to a higher number of preapoptotic cells. These changes were associated with higher expression of \n<jats:italic>Adamst\u20105<\/jats:italic>, suggesting higher cartilage degradation, and with low expression levels of \n<jats:italic>Igf1<\/jats:italic> and \n<jats:italic>Col2<\/jats:italic> that reflect the decreased growth ability of diabetic mice. \n<jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup> bone morphology was characterized by low cortical bone area (Ct.Ar) but higher trabecular bone volume (BV\/TV) and expression analysis showed a downregulation of bone markers \n<jats:italic>Acp5<\/jats:italic>, \n<jats:italic>Oc<\/jats:italic>, and \n<jats:italic>Runx2<\/jats:italic>. Serum levels of insulin and leptin were found to be reduced at all\u2010time points \n<jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup>. We suggest that \n<jats:italic>Ins2<\/jats:italic>\n<jats:sup><jats:italic>Akita<\/jats:italic><\/jats:sup> mice bone phenotype is caused by lower bone formation and even lower bone resorption due to insulin deficiency and to a possible relation with low leptin signaling.<\/jats:p>","DOI":"10.1002\/jcp.27617","type":"journal-article","created":{"date-parts":[[2018,10,14]],"date-time":"2018-10-14T10:37:18Z","timestamp":1539513438000},"page":"9338-9350","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Altered bone microarchitecture in a type 1 diabetes mouse model <i>Ins2<\/i><sup><i>Akita<\/i><\/sup>"],"prefix":"10.1002","volume":"234","author":[{"given":"Filipe R.","family":"Carvalho","sequence":"first","affiliation":[{"name":"Centre of Marine Sciences (CCMAR), Universidade do Algarve Faro Portugal"},{"name":"PhD Program in Biomedical Sciences, Universidade do Algarve Faro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia M.","family":"Calado","sequence":"additional","affiliation":[{"name":"PhD Program in Biomedical Sciences, Universidade do Algarve Faro Portugal"},{"name":"Centre for Biomedical Research (CBMR), University of Algarve Faro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela A.","family":"Silva","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Research (CBMR), University of Algarve Faro Portugal"},{"name":"Department of Biomedical Sciences and Medicine\u2010DCBM Universidade do Algarve Faro Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela S.","family":"Diogo","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s \u2013 PT Government Associate Laboratory Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joana","family":"Moreira da Silva","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s \u2013 PT Government Associate Laboratory Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui L.","family":"Reis","sequence":"additional","affiliation":[{"name":"ICVS\/3B\u2019s \u2013 PT Government Associate Laboratory Guimar\u00e3es Portugal"},{"name":"3B\u2019s Research Group\u2010Biomaterials, Biodegradables and Biomimetics, Universidade do Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine Guimar\u00e3es Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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