{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:30:21Z","timestamp":1788928221816,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2015,6,16]],"date-time":"2015-06-16T00:00:00Z","timestamp":1434412800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001632","name":"University of Ulster","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001632","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008302","name":"Department of Education and Learning, Northern Ireland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008302","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NV Organon"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2015,8]]},"abstract":"\n Aims<\/jats:title>\n \n To examine the biological characteristics of a novel glucagon\u2010like peptide\u20101 (\n GLP<\/jats:styled-content>\n \u20101) conjugate, in which an antithrombin\n III<\/jats:styled-content>\n (\n ATIII<\/jats:styled-content>\n )\u2010binding pentasaccharide is conjugated to\n d<\/jats:sc>\n \u2010\n \n Ala\n 8<\/jats:sup>\n GLP\n <\/jats:styled-content>\n \u20101 using a tetraethylene glycol linker.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We assessed\n GLP<\/jats:styled-content>\n \u20101 receptor binding,\n cAMP<\/jats:styled-content>\n generation and insulin secretory activity of the\n GLP<\/jats:styled-content>\n \u20101 conjugate\n in vitro<\/jats:italic>\n . Circulating half\u2010life, glucose homeostatic and subchronic therapeutic effectiveness were then examined\n in vivo<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The half\u2010life of the\n GLP<\/jats:styled-content>\n \u20101 conjugate in mice was \u223c11\u2009h.\n In vitro<\/jats:italic>\n insulin secretion from clonal \u03b2 cells and islets was increased (p\u2009<\u20090.001) by the conjugate. The conjugate had half maximum effective concentration values of 1.3\u2009\u00d7\u200910\n \u22127<\/jats:sup>\n and 9.9\u2009\u00d7\u200910\n \u22128<\/jats:sup>\n \u2009M for displacement of\n \n 125<\/jats:sup>\n I\u2010GLP\n <\/jats:styled-content>\n \u20101 in competitive\n GLP<\/jats:styled-content>\n \u20101 receptor binding and\n cAMP<\/jats:styled-content>\n generation, respectively. Glucose tolerance in normal mice, immediately and 4\u2009h after conjugate injection, resulted in significant (p\u2009<\u20090.001) improvements in blood glucose. These effects persisted for >48\u2009h after administration. Daily treatment (21\u2009days) of high\u2010fat\u2010fed and\n ob\/ob<\/jats:italic>\n mice with 25\u2009nmol\/kg conjugate resulted in significant improvement in glucose tolerance (p\u2009<\u20090.001) and reductions in glycated haemoglobin (\n HbA1c<\/jats:styled-content>\n ; p\u2009<\u20090.01) equivalent to or better than with exenatide or liraglutide. Treatment of\n C57BL<\/jats:styled-content>\n \/\n KsJ<\/jats:styled-content>\n db\/db<\/jats:italic>\n mice for 15\u2009days with 100\u2009nmol\/kg conjugate significantly (p\u2009<\u20090.001) reduced glucose and raised plasma insulin. Oral glucose tolerance was significantly (p\u2009<\u20090.001) improved and both 24\u2010h glucose profile (p\u2009<\u20090.001) and\n HbA1c<\/jats:styled-content>\n levels (p\u2009<\u20090.001) were reduced. Islet size (p\u2009<\u20090.001) and pancreatic insulin content were increased without change of islet cell proliferation or apoptosis.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These data show that\n d<\/jats:sc>\n \u2010\n \n Ala\n 8<\/jats:sup>\n GLP\u20101\n <\/jats:styled-content>\n (\n \n Lys\n 37<\/jats:sup>\n <\/jats:styled-content>\n ) pentasaccharide exerts significant antidiabetic actions and has a projected pharmacokinetic\/pharmacodynamic profile that merits further evaluation in humans for a possible once\u2010weekly dosing regimen.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/dom.12483","type":"journal-article","created":{"date-parts":[[2015,4,30]],"date-time":"2015-04-30T04:51:53Z","timestamp":1430369513000},"page":"760-770","source":"Crossref","is-referenced-by-count":6,"title":["Pharmacological characterization and antidiabetic activity of a long\u2010acting glucagon\u2010like peptide\u20101 analogue conjugated to an antithrombin\n III<\/scp>\n \u2010binding pentasaccharide"],"prefix":"10.1111","volume":"17","author":[{"given":"S.","family":"Patterson","sequence":"first","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes, University of Ulster Coleraine UK"},{"name":"Department of Life Sciences School of Health and Life Sciences, Glasgow Caledonian University Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"de Kort","sequence":"additional","affiliation":[{"name":"MSD Oss The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Irwin","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes, University of Ulster Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. C.","family":"Moffett","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes, University of Ulster Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. H. A.","family":"Dokter","sequence":"additional","affiliation":[{"name":"MSD Oss The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. S.","family":"Bos","sequence":"additional","affiliation":[{"name":"MSD Oss The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. M. M.","family":"Miltenburg","sequence":"additional","affiliation":[{"name":"MSD Oss The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. R.","family":"Flatt","sequence":"additional","affiliation":[{"name":"SAAD Centre for Pharmacy and Diabetes, University of Ulster Coleraine UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,6,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.054"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2007.09.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01628.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2741\/2799"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3809"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01574.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200800053"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04460.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2009.01036.x"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/352760068X"},{"key":"e_1_2_7_12_1","volume-title":"Chemistry of Peptide Synthesis","author":"Benoiton NL","year":"2005"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","DOI":"10.1385\/1592598137","volume-title":"Bioconjugation Protocols Strategies and Methods","author":"Niemeyer CM","year":"2004"},{"key":"e_1_2_7_14_1","volume-title":"Bioconjugate Techniques","author":"Hermanson GT","year":"2008"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0509997"},{"key":"e_1_2_7_16_1","first-page":"161","volume-title":"R1A and Related Procedures Medicine","author":"Paus E","year":"1982"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.512046"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2337\/diab.45.8.1132"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00252768"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12300"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0078560"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddtec.2006.03.001"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01687.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.50.11.2530"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1900\/RDS.2011.8.307"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.14.7.847"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1507"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.53.suppl_3.S205"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.04.063"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/dcS13-2015"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(87)91194-9"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01222201"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0323"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.12.093"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fdom.12483","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.12483","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T05:16:30Z","timestamp":1761887790000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.12483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,16]]},"references-count":33,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2015,8]]}},"alternative-id":["10.1111\/dom.12483"],"URL":"https:\/\/doi.org\/10.1111\/dom.12483","archive":["Portico"],"relation":{},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,16]]}}}