{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T13:04:17Z","timestamp":1783947857096,"version":"3.55.0"},"reference-count":19,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2011,10,1]],"date-time":"2011-10-01T00:00:00Z","timestamp":1317427200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cell Transplant"],"published-print":{"date-parts":[[2011,10]]},"abstract":"<jats:p>Combination therapy with a dipeptidyl peptidase-4 inhibitor (DPP-4i) and a proton pump inhibitor (PPI) raises endogenous levels of GLP-1 and gastrin, respectively, and restores pancreatic \u03b2-cell mass and normoglycemia in nonobese diabetic (NOD) mice with autoimmune diabetes. The aim of this study was to determine whether a DPP-4i and PPI combination could increase \u03b2-cell mass in the adult human pancreas. Pancreatic cells from adult human pancreas donors were implanted in NOD-severe combined immunodeficient (NOD-scid) mice and the mice were treated with a DPP-4i and a PPI for 16 weeks. Human grafts were examined for insulin content and insulin-stained cells. Graft \u03b2-cell function was assessed by intravenous glucose tolerance tests (IVGTT) and by glucose control in human cell-engrafted mice treated with streptozotocin (STZ) to delete mouse pancreatic \u03b2-cells. Plasma GLP-1 and gastrin levels were raised to two- to threefold in DPP-4i- and PPI-treated mice. Insulin content and insulin-stained cells in human pancreatic cell grafts were increased 9- to 13-fold in DPP-4i and PPI-treated mice and insulin-stained cells were colocalized with pancreatic exocrine duct cells. Plasma human C-peptide responses to IVGTT were significantly higher and STZ-induced hyperglycemia was more completely prevented in DPP-4i- and PPI-treated mice with grafts than in vehicle-treated mice with grafts. In conclusion, DPP-4i and PPI combination therapy raises endogenous levels of GLP-1 and gastrin and greatly expands the functional \u03b2-cell mass in adult human pancreatic cells implanted in immunodeficient mice, largely from pancreatic duct cells. This suggests that a DPP-4i and PPI combination treatment may provide a pharmacologic therapy to correct the \u03b2-cell deficit in type 1 diabetes.<\/jats:p>","DOI":"10.3727\/096368910x557263","type":"journal-article","created":{"date-parts":[[2011,11,14]],"date-time":"2011-11-14T10:06:13Z","timestamp":1321265173000},"page":"1343-1350","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Combination Therapy with a Dipeptidyl Peptidase-4 Inhibitor and a Proton Pump Inhibitor Induces \u03b2-Cell Neogenesis from Adult Human Pancreatic Duct Cells Implanted in Immunodeficient Mice"],"prefix":"10.1177","volume":"20","author":[{"given":"Wilma L.","family":"Suarez-Pinzon","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, AB, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Sanford Research, University of South Dakota, Sioux Falls, SD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,10,1]]},"reference":[{"key":"bibr1-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69705-5"},{"key":"bibr2-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-003-1241-2"},{"key":"bibr3-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1038\/nm1367"},{"key":"bibr4-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1210\/endo.136.8.7628397"},{"key":"bibr5-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/db09-1618"},{"key":"bibr6-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1177\/096368979900800309"},{"key":"bibr7-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-008-1105-x"},{"key":"bibr8-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0b013e3283337e1c"},{"key":"bibr9-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/db05-1602"},{"key":"bibr10-096368910X557263","doi-asserted-by":"publisher","DOI":"10.3727\/096368910X509004"},{"key":"bibr11-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.3.741"},{"key":"bibr12-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.51.3.686"},{"key":"bibr13-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-009-1390-z"},{"key":"bibr14-096368910X557263","doi-asserted-by":"publisher","DOI":"10.3727\/096368908786092775"},{"key":"bibr15-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0688"},{"key":"bibr16-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0068"},{"key":"bibr17-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/diab.41.1.114"},{"key":"bibr18-096368910X557263","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116708"},{"key":"bibr19-096368910X557263","doi-asserted-by":"publisher","DOI":"10.2337\/db06-1670"}],"container-title":["Cell Transplantation"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3727\/096368910X557263","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/full-xml\/10.3727\/096368910X557263","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/journals.sagepub.com\/doi\/pdf\/10.3727\/096368910X557263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T15:37:02Z","timestamp":1777390622000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.sagepub.com\/doi\/10.3727\/096368910X557263"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,10]]}},"alternative-id":["10.3727\/096368910X557263"],"URL":"https:\/\/doi.org\/10.3727\/096368910x557263","relation":{},"ISSN":["0963-6897","1555-3892"],"issn-type":[{"value":"0963-6897","type":"print"},{"value":"1555-3892","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10]]}}}