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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...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
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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 |
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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 |
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