{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:55:13Z","timestamp":1785851713500,"version":"3.56.0"},"reference-count":61,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T00:00:00Z","timestamp":1388361600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Plant Biotechnology Journal"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The incretin hormone glucagon\u2010like peptide\u20101 (<jats:styled-content style=\"fixed-case\">GLP<\/jats:styled-content>\u20101) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin\u20104) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin\u20104 (Ex\u20104) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex\u20104 coupled with human transferrin (Ex\u20104\u2010Tf) and its characterization. We demonstrated that plant\u2010made Ex\u20104\u2010Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic \u03b2\u2010cells, promoted \u03b2\u2010cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin\u2010producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex\u20104\u2010Tf significantly improved glucose tolerance, whereas commercial Ex\u20104 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>) injection of Ex\u20104\u2010Tf showed a beneficial effect in mice similar to<jats:styled-content style=\"fixed-case\">IP<\/jats:styled-content>\u2010injected Ex\u20104. We also showed that plants provide a robust system for the expression of Ex\u20104\u2010Tf, producing up to 37\u00a0\u03bcg prEx\u20104\u2010Tf\/g fresh leaf weight in transgenic tobacco and 137\u00a0\u03bcg prEx\u20104\u2010Tf\/g freshweight in transiently transformed leaves of<jats:italic>N.\u00a0benthamiana<\/jats:italic>. These results indicate that Ex\u20104\u2010Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx\u20104\u2010Tf in plants may offer a convenient and cost\u2010effective method to deliver the antidiabetic medicine in partially processed plant food products.<\/jats:p>","DOI":"10.1111\/pbi.12149","type":"journal-article","created":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T08:12:43Z","timestamp":1388391163000},"page":"425-435","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes"],"prefix":"10.1111","volume":"12","author":[{"given":"Jeehye","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Biology University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Diao","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Chao","family":"Feng","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute London ON Canada"},{"name":"Department of Physiology &amp; Pharmacology University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rennian","family":"Wang","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute London ON Canada"},{"name":"Department of Physiology &amp; Pharmacology University of Western Ontario London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony M.","family":"Jevnikar","sequence":"additional","affiliation":[{"name":"Lawson Health Research Institute London ON Canada"},{"name":"Plantigen Inc. London ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengwu","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Biology University of Western Ontario London ON Canada"},{"name":"Lawson Health Research Institute London ON Canada"},{"name":"Plantigen Inc. 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