Cargando…

Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor

BACKGROUND: Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated by dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, a...

Descripción completa

Detalles Bibliográficos
Autores principales: Ansarullah, Lu, Yan, Holstein, Martha, DeRuyter, Brittany, Rabinovitch, Alex, Guo, Zhiguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558424/
https://www.ncbi.nlm.nih.gov/pubmed/23382843
http://dx.doi.org/10.1371/journal.pone.0053345
_version_ 1782257433104613376
author Ansarullah,
Lu, Yan
Holstein, Martha
DeRuyter, Brittany
Rabinovitch, Alex
Guo, Zhiguang
author_facet Ansarullah,
Lu, Yan
Holstein, Martha
DeRuyter, Brittany
Rabinovitch, Alex
Guo, Zhiguang
author_sort Ansarullah,
collection PubMed
description BACKGROUND: Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated by dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, a DPP-IV inhibitor, on β-cell regeneration in diabetic mice. MATERIALS & METHODS: Diabetes in C57BL/6 mice was induced by streptozotocin. PSN632408 and sitagliptin alone or in combination were administered to diabetic mice for 7 weeks along with BrdU daily. Nonfasting blood glucose levels were monitored. After treatment, oral glucose tolerance test (OGTT), plasma active GLP-1 levels, β-cell mass along with α- and β-cell replication, and β-cell neogenesis were evaluated. RESULTS: Normoglycemia was not achieved in vehicle-treated mice. By contrast, 32% (6 of 19) of PSN632408-treated diabetic mice, 36% (5 of 14) sitagliptin-treated diabetic mice, and 59% (13 of 22) diabetic mice treated with PSN632408 and sitagliptin combination achieved normoglycemia after 7 weeks treatment. Combination therapy significantly increased plasma active GLP-1 levels, improved glucose clearance, stimulated both α- and β-cell replication, and augmented β-cell mass. Furthermore, treatment with combination therapy induced β-cell neogenesis from pancreatic duct-derived cells. CONCLUSION: Our results demonstrate that combining a GPR119 agonist with a DPP-IV inhibitor may offer a novel therapeutic strategy for stimulating β-cell regeneration and reversing diabetes.
format Online
Article
Text
id pubmed-3558424
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-35584242013-02-04 Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor Ansarullah, Lu, Yan Holstein, Martha DeRuyter, Brittany Rabinovitch, Alex Guo, Zhiguang PLoS One Research Article BACKGROUND: Activating G-protein coupled receptor 119 (GPR119) by its agonists can stimulate glucagon like peptide-1 (GLP-1) release. GLP-1 is rapidly degraded and inactivated by dipeptidylpeptidase-IV (DPP-IV). We studied the efficiency of combining PSN632408, a GPR119 agonist, with sitagliptin, a DPP-IV inhibitor, on β-cell regeneration in diabetic mice. MATERIALS & METHODS: Diabetes in C57BL/6 mice was induced by streptozotocin. PSN632408 and sitagliptin alone or in combination were administered to diabetic mice for 7 weeks along with BrdU daily. Nonfasting blood glucose levels were monitored. After treatment, oral glucose tolerance test (OGTT), plasma active GLP-1 levels, β-cell mass along with α- and β-cell replication, and β-cell neogenesis were evaluated. RESULTS: Normoglycemia was not achieved in vehicle-treated mice. By contrast, 32% (6 of 19) of PSN632408-treated diabetic mice, 36% (5 of 14) sitagliptin-treated diabetic mice, and 59% (13 of 22) diabetic mice treated with PSN632408 and sitagliptin combination achieved normoglycemia after 7 weeks treatment. Combination therapy significantly increased plasma active GLP-1 levels, improved glucose clearance, stimulated both α- and β-cell replication, and augmented β-cell mass. Furthermore, treatment with combination therapy induced β-cell neogenesis from pancreatic duct-derived cells. CONCLUSION: Our results demonstrate that combining a GPR119 agonist with a DPP-IV inhibitor may offer a novel therapeutic strategy for stimulating β-cell regeneration and reversing diabetes. Public Library of Science 2013-01-29 /pmc/articles/PMC3558424/ /pubmed/23382843 http://dx.doi.org/10.1371/journal.pone.0053345 Text en © 2013 Ansarullah et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ansarullah,
Lu, Yan
Holstein, Martha
DeRuyter, Brittany
Rabinovitch, Alex
Guo, Zhiguang
Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title_full Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title_fullStr Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title_full_unstemmed Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title_short Stimulating β-Cell Regeneration by Combining a GPR119 Agonist with a DPP-IV Inhibitor
title_sort stimulating β-cell regeneration by combining a gpr119 agonist with a dpp-iv inhibitor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3558424/
https://www.ncbi.nlm.nih.gov/pubmed/23382843
http://dx.doi.org/10.1371/journal.pone.0053345
work_keys_str_mv AT ansarullah stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor
AT luyan stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor
AT holsteinmartha stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor
AT deruyterbrittany stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor
AT rabinovitchalex stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor
AT guozhiguang stimulatingbcellregenerationbycombiningagpr119agonistwithadppivinhibitor