Show simple item record

dc.contributor.authorYang, Chaoxing
dc.contributor.authorLoehn, Matthias
dc.contributor.authorJurczyk, Agata
dc.contributor.authorPrzewozniak, Natalia
dc.contributor.authorLeehy, Linda
dc.contributor.authorHerrera, Pedro L.
dc.contributor.authorShultz, Leonard D.
dc.contributor.authorGreiner, Dale L.
dc.contributor.authorHarlan, David
dc.contributor.authorBortell, Rita
dc.date2022-08-11T08:09:44.000
dc.date.accessioned2022-08-23T16:41:11Z
dc.date.available2022-08-23T16:41:11Z
dc.date.issued2015-08-20
dc.date.submitted2015-12-08
dc.identifier.citationDiabetes Metab Syndr Obes. 2015 Aug 20;8:387-98. doi: 10.2147/DMSO.S87253. eCollection 2015. <a href="http://dx.doi.org/10.2147/DMSO.S87253">Link to article on publisher's site</a>
dc.identifier.issn1178-7007 (Linking)
dc.identifier.doi10.2147/DMSO.S87253
dc.identifier.pmid26316789
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39834
dc.description.abstractOBJECTIVE: Glucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and survival in vivo. METHODS: Five independent transplant studies were conducted with human islets from five individual donors. Diabetic human islet-engrafted immunodeficient mice were treated with lixisenatide (50, 150, and 500 microg/kg) or vehicle. Islet function was determined by blood glucose, plasma human insulin/C-peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and alpha-cell number, percent proliferation, and levels of apoptosis. RESULTS: Diabetic mice transplanted with marginal human islet mass and treated with lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice. Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of lixisenatide-treated mice were significantly improved compared to vehicle-treated mice. The percentages of proliferating or apoptotic beta cells at graft recovery were not different between lixisenatide-treated and vehicle-treated mice. Nevertheless, in one experiment we found a significant twofold to threefold increase in human beta-cell numbers in lixisenatide-treated compared to vehicle-treated mice. CONCLUSION: Diabetic human islet-engrafted immunodeficient mice treated with lixisenatide show improved restoration of normoglycemia, human plasma insulin, and glucose tolerance compared to vehicle-treated mice engrafted with the same donor islets. Because the proliferative capacity of human beta cells is limited, improved beta-cell survival coupled with enhanced beta-cell function following lixisenatide treatment may provide the greatest benefit for diabetic patients with reduced functional islet mass.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=26316789&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 2015 Yang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at <a href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</a>. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/
dc.subjectGLP-1 receptor agonist
dc.subjectlixisenatide
dc.subjecthuman islet transplant
dc.subjectbeta cells
dc.subjectglucose tolerance tests
dc.subjectplasma insulin
dc.subjectEndocrine System Diseases
dc.subjectEndocrinology
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.titleLixisenatide accelerates restoration of normoglycemia and improves human beta-cell function and survival in diabetic immunodeficient NOD-scid IL-2rg(null) RIP-DTR mice engrafted with human islets
dc.typeJournal Article
dc.source.journaltitleDiabetes, metabolic syndrome and obesity : targets and therapy
dc.source.volume8
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3634&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2630
dc.identifier.contextkey7920051
refterms.dateFOA2022-08-23T16:41:12Z
html.description.abstract<p>OBJECTIVE: Glucagon-like peptide-1 induces glucose-dependent insulin secretion and, in rodents, increases proliferation and survival of pancreatic beta cells. To investigate the effects on human beta cells, we used immunodeficient mice transplanted with human islets. The goal was to determine whether lixisenatide, a glucagon-like peptide-1 receptor agonist, improves human islet function and survival in vivo.</p> <p>METHODS: Five independent transplant studies were conducted with human islets from five individual donors. Diabetic human islet-engrafted immunodeficient mice were treated with lixisenatide (50, 150, and 500 microg/kg) or vehicle. Islet function was determined by blood glucose, plasma human insulin/C-peptide, and glucose tolerance tests. Grafts were analyzed for total beta- and alpha-cell number, percent proliferation, and levels of apoptosis.</p> <p>RESULTS: Diabetic mice transplanted with marginal human islet mass and treated with lixisenatide were restored to euglycemia more rapidly than vehicle-treated mice. Glucose tolerance tests, human plasma insulin, and glucose-stimulation indices of lixisenatide-treated mice were significantly improved compared to vehicle-treated mice. The percentages of proliferating or apoptotic beta cells at graft recovery were not different between lixisenatide-treated and vehicle-treated mice. Nevertheless, in one experiment we found a significant twofold to threefold increase in human beta-cell numbers in lixisenatide-treated compared to vehicle-treated mice.</p> <p>CONCLUSION: Diabetic human islet-engrafted immunodeficient mice treated with lixisenatide show improved restoration of normoglycemia, human plasma insulin, and glucose tolerance compared to vehicle-treated mice engrafted with the same donor islets. Because the proliferative capacity of human beta cells is limited, improved beta-cell survival coupled with enhanced beta-cell function following lixisenatide treatment may provide the greatest benefit for diabetic patients with reduced functional islet mass.</p>
dc.identifier.submissionpathoapubs/2630
dc.contributor.departmentDepartment of Medicine
dc.contributor.departmentDiabetes Center of Excellence
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages387-98


Files in this item

Thumbnail
Name:
DMSO_87253_lixisenatide_accele ...
Size:
2.685Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

Copyright © 2015 Yang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at <a href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</a>. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
Except where otherwise noted, this item's license is described as Copyright © 2015 Yang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at <a href="http://creativecommons.org/licenses/by-nc/3.0/">http://creativecommons.org/licenses/by-nc/3.0/</a>. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.