{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:28:37Z","timestamp":1694658517043},"reference-count":17,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2011,7]]},"abstract":"<jats:p>Recently, we reported the generation of single-chain antibodies (SCAs) highly specific for rodent and human \u03b2-cells. Our current report describes the generation of a fusion protein of one of these SCAs (SCA B1) with a NF-\u03baB essential modifier (NEMO)-binding domain (NBD) peptide, thereby creating a selective inhibitor of NF-\u03baB activation in \u03b2-cells. The SCA B1-NBD fusion protein was cloned in the pIRES-EGFP, expressed in bacteria, and purified by metal affinity chromatography; the newly generated complex was then administered intravenously to rodents and evaluated for its ability to protect \u03b2-cells against cytokines in vitro and diabetogenic agents in vivo. First, it was shown clearly that our SCA B1-NBD fusion protein binds highly selective to CD rat \u03b2-cells in vivo. Second, we observed that SCA B1-mediated in vivo delivery of the NBD peptide completely blocked IL-1\u03b2 + IFN\u03b3- and TNF\u03b1 + IFN\u03b3-mediated induction of NF-\u03baB as well as islet dysfunction in culture. Finally, repeated intravenous injection of SCA B1-NBD prior to multiple low-dose administration of streptozotocin in CD mice not only induced a striking resistance to diabetes development but also preserved \u03b2-cell mass. In conclusion, our data show for the first time that a SCA B1-NBD fusion peptide reliably protects \u03b2-cells against cytokines in vitro and allows protection from diabetes development in CD mice in vivo.<\/jats:p>","DOI":"10.1152\/ajpendo.00603.2010","type":"journal-article","created":{"date-parts":[[2011,4,27]],"date-time":"2011-04-27T02:03:30Z","timestamp":1303869810000},"page":"E83-E90","source":"Crossref","is-referenced-by-count":6,"title":["Protection from diabetes development by single-chain antibody-mediated delivery of a NF-\u03baB inhibitor specifically to \u03b2-cells in vivo"],"prefix":"10.1152","volume":"301","author":[{"given":"Sandra","family":"Ueberberg","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Metabolism, Berufsgenossenschaftliches University Hospital Bergmannsheil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timo","family":"Deutschbein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Metabolism, Berufsgenossenschaftliches University Hospital Bergmannsheil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harald H.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Metabolism, Berufsgenossenschaftliches University Hospital Bergmannsheil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johannes W.","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Metabolism, Berufsgenossenschaftliches University Hospital Bergmannsheil;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara","family":"Akinturk","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy and Molecular Brain Research, Ruhr-University, Bochum, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nora","family":"Prochnow","sequence":"additional","affiliation":[{"name":"Department of Neuroanatomy and Molecular Brain Research, Ruhr-University, Bochum, Germany;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"Schirrmacher","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec, Canada; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Schneider","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Division of Endocrinology and Metabolism, Berufsgenossenschaftliches University Hospital Bergmannsheil;"},{"name":"Medical Department II, Diabetology and Endocrinology, St. Vinzenz Hospital, Cologne, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.1.102"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0783"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(99)00018-2"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s001250100021"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508166103"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005943200"},{"key":"B7","doi-asserted-by":"crossref","first-page":"410","DOI":"10.4049\/jimmunol.160.1.410","volume":"160","author":"Jobin C","year":"1998","journal-title":"J Immunol"},{"key":"B7a","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1650093"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1126\/science.289.5484.1550"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00315.2010"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.2.1526"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-0999-7"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M207700200"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.3.687"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1725-9"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0658"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2337\/diab.39.4.401"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00603.2010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T13:55:22Z","timestamp":1686059722000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00603.2010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,7]]},"references-count":17,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2011,7]]}},"alternative-id":["10.1152\/ajpendo.00603.2010"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00603.2010","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,7]]}}}