{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T12:00:11Z","timestamp":1778155211367,"version":"3.51.4"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Vascular calcification (VC) is inhibited by the glycoprotein osteoprotegerin (OPG). It is unclear whether treatments for type 2 diabetes are capable of promoting or inhibiting VC. The present study examined the effects of insulin and liraglutide on i) the production of OPG and ii) the emergence of VC, both<jats:italic>in vitro<\/jats:italic>in human aortic smooth muscle cells (HASMCs) and<jats:italic>in vivo<\/jats:italic>in type 2 diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design\/methods<\/jats:title><jats:p>HASMCs were exposed to insulin glargine or liraglutide, after which OPG production, alkaline phosphatase (<jats:italic>ALP<\/jats:italic>) activity and levels of<jats:italic>Runx2<\/jats:italic>,<jats:italic>ALP<\/jats:italic>and bone sialoprotein (<jats:italic>BSP<\/jats:italic>) mRNA were measured. A prospective, nonrandomised human subject study was also conducted, in which OPG levels and coronary artery calcification (CAC) were measured in a type 2 diabetes population before and 16 months after the commencement of either insulin or liraglutide treatment and in a control group that took oral hypoglycemics only.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure to insulin glargine, but not liraglutide, was associated with significantly decreased OPG production (11\u200a913\u00b11409\u200apg\/10<jats:sup>4<\/jats:sup>cells vs 282\u00b113\u200apg\/10<jats:sup>4<\/jats:sup>cells, control vs 10\u200anmol\/l insulin,<jats:italic>P<\/jats:italic>&lt;0.0001), increased<jats:italic>ALP<\/jats:italic>activity (0.82\u00b10.06 IU\/10<jats:sup>4<\/jats:sup>cells vs 2.40\u00b10.16\u200aIU\/10<jats:sup>4<\/jats:sup>cells, control vs 10\u200anmol\/l insulin,<jats:italic>P<\/jats:italic>&lt;0.0001) and increased osteogenic gene expression by HASMCs. In the clinical study (<jats:italic>n<\/jats:italic>=101), insulin treatment was associated with a significant reduction in OPG levels and, despite not achieving full statistical significance, a trend towards increased CAC in patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Exogenous insulin down-regulated OPG<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>and promoted VC<jats:italic>in vitro<\/jats:italic>. Although neither insulin nor liraglutide significantly affected CAC in the present pilot study, these data support the establishment of randomised trials to investigate medications and VC in diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1530\/eje-14-1137","type":"journal-article","created":{"date-parts":[[2015,6,3]],"date-time":"2015-06-03T14:08:25Z","timestamp":1433340505000},"page":"53-61","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":17,"title":["The effects of insulin and liraglutide on osteoprotegerin and vascular calcification in vitro and in patients with type 2 diabetes"],"prefix":"10.1093","volume":"173","author":[{"given":"Colin","family":"Davenport","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan A","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Forde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David T","family":"Ashley","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amar","family":"Agha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"McDermott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seamus","family":"Sreenan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank","family":"McGrath","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan","family":"McAdam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip M","family":"Cummins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diarmuid","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","reference":[{"issue":"10","key":"1_22927993","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1161\/01.RES.0000249379.55535.21","volume":"99","author":"Johnson","year":"2006","journal-title":"Circulation Research","ISSN":"https:\/\/id.crossref.org\/issn\/0009-7330","issn-type":"print"},{"issue":"7","key":"2_18383779","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1161\/01.ATV.0000133194.94939.42","volume":"24","year":"2004","journal-title":"Arteriosclerosis, Thrombosis, and Vascular Biology","ISSN":"https:\/\/id.crossref.org\/issn\/0276-5047","issn-type":"print"},{"issue":"2","key":"3_11025710","doi-asserted-by":"publisher","first-page":"335","DOI":"10.2337\/diacare.24.2.335","volume":"24","author":"Schurgin","year":"2001","journal-title":"Diabetes Care","ISSN":"https:\/\/id.crossref.org\/issn\/0149-5992","issn-type":"print"},{"issue":"3","key":"4_42344814","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1007\/s11906-012-0265-8","volume":"14","author":"Chen","year":"2012","journal-title":"Current hypertension reports","ISSN":"https:\/\/id.crossref.org\/issn\/1522-6417","issn-type":"print"},{"issue":"9","key":"5_5994672","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1101\/gad.12.9.1260","volume":"12","author":"Bucay","year":"1998","journal-title":"Genes &amp; Development","ISSN":"https:\/\/id.crossref.org\/issn\/0890-9369","issn-type":"print"},{"issue":"7","key":"6_23131359","doi-asserted-by":"publisher","first-page":"395","DOI":"10.2310\/6650.2006.06019","volume":"54","author":"Tintut","year":"2006","journal-title":"Journal of investigative medicine : the official publication of the American Federation for Clinical Research","ISSN":"https:\/\/id.crossref.org\/issn\/1081-5589","issn-type":"print"},{"issue":"1","key":"7_34621730","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1530\/EJE-09-0141","volume":"161","year":"2009","journal-title":"European Journal of Endocrinology","ISSN":"https:\/\/id.crossref.org\/issn\/0804-4643","issn-type":"print"},{"issue":"6","key":"8_34073577","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1007\/s00223-009-9220-3","volume":"84","author":"Nuche-Berenguer","year":"2009","journal-title":"Calcified Tissue International","ISSN":"https:\/\/id.crossref.org\/issn\/1432-0827","issn-type":"print"},{"key":"9_22832278","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00047.2006","year":"2006","journal-title":"American Journal of Physiology - 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