Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice
Summary: Under extreme conditions or by genetic modification, pancreatic α-cells can regenerate and be converted into β-cells. This regeneration holds substantial promise for cell replacement therapy in diabetic patients. The discovery of clinical therapeutic strategies to promote β-cell regeneratio...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-06-01
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| Series: | iScience |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004219301671 |
| _version_ | 1819027958255321088 |
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| author | Rui Wei Liangbiao Gu Jin Yang Kun Yang Junling Liu Yunyi Le Shan Lang Haining Wang Dung Thai Hai Yan Tianpei Hong |
| author_facet | Rui Wei Liangbiao Gu Jin Yang Kun Yang Junling Liu Yunyi Le Shan Lang Haining Wang Dung Thai Hai Yan Tianpei Hong |
| author_sort | Rui Wei |
| collection | DOAJ |
| description | Summary: Under extreme conditions or by genetic modification, pancreatic α-cells can regenerate and be converted into β-cells. This regeneration holds substantial promise for cell replacement therapy in diabetic patients. The discovery of clinical therapeutic strategies to promote β-cell regeneration is crucial for translating these findings into clinical applications. In this study, we reported that treatment with REMD 2.59, a human glucagon receptor (GCGR) monoclonal antibody (mAb), lowered blood glucose without inducing hypoglycemia in normoglycemic, streptozotocin-induced type 1 diabetic (T1D) and non-obesity diabetic mice. Moreover, GCGR mAb treatment increased the plasma glucagon and active glucagon-like peptide-1 levels, induced pancreatic ductal ontogenic α-cell neogenesis, and promoted α-cell proliferation. Strikingly, the treatment also increased the β-cell mass in these two T1D models. Using α-cell lineage-tracing mice, we found that the neogenic β-cells were likely derived from α-cell conversion. Therefore, GCGR mAb-induced α- to β-cell conversion might represent a pre-clinical approach for improving diabetes therapy. : Diabetology; Endocrinology; Specialized Functions of Cells Subject Areas: Diabetology, Endocrinology, Specialized Functions of Cells |
| first_indexed | 2024-12-21T05:50:44Z |
| format | Article |
| id | doaj.art-88628399c772456ea58aaf4df078709e |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-12-21T05:50:44Z |
| publishDate | 2019-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-88628399c772456ea58aaf4df078709e2022-12-21T19:13:59ZengElsevieriScience2589-00422019-06-0116326339Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic MiceRui Wei0Liangbiao Gu1Jin Yang2Kun Yang3Junling Liu4Yunyi Le5Shan Lang6Haining Wang7Dung Thai8Hai Yan9Tianpei Hong10Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, ChinaREMD Biotherapeutics, Camarillo, CA 93012, USA; Beijing Cosci-REMD, Beijing 102206, ChinaREMD Biotherapeutics, Camarillo, CA 93012, USA; Beijing Cosci-REMD, Beijing 102206, ChinaDepartment of Endocrinology and Metabolism, Peking University Third Hospital, Beijing 100191, China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China; Corresponding authorSummary: Under extreme conditions or by genetic modification, pancreatic α-cells can regenerate and be converted into β-cells. This regeneration holds substantial promise for cell replacement therapy in diabetic patients. The discovery of clinical therapeutic strategies to promote β-cell regeneration is crucial for translating these findings into clinical applications. In this study, we reported that treatment with REMD 2.59, a human glucagon receptor (GCGR) monoclonal antibody (mAb), lowered blood glucose without inducing hypoglycemia in normoglycemic, streptozotocin-induced type 1 diabetic (T1D) and non-obesity diabetic mice. Moreover, GCGR mAb treatment increased the plasma glucagon and active glucagon-like peptide-1 levels, induced pancreatic ductal ontogenic α-cell neogenesis, and promoted α-cell proliferation. Strikingly, the treatment also increased the β-cell mass in these two T1D models. Using α-cell lineage-tracing mice, we found that the neogenic β-cells were likely derived from α-cell conversion. Therefore, GCGR mAb-induced α- to β-cell conversion might represent a pre-clinical approach for improving diabetes therapy. : Diabetology; Endocrinology; Specialized Functions of Cells Subject Areas: Diabetology, Endocrinology, Specialized Functions of Cellshttp://www.sciencedirect.com/science/article/pii/S2589004219301671 |
| spellingShingle | Rui Wei Liangbiao Gu Jin Yang Kun Yang Junling Liu Yunyi Le Shan Lang Haining Wang Dung Thai Hai Yan Tianpei Hong Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice iScience |
| title | Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice |
| title_full | Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice |
| title_fullStr | Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice |
| title_full_unstemmed | Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice |
| title_short | Antagonistic Glucagon Receptor Antibody Promotes α-Cell Proliferation and Increases β-Cell Mass in Diabetic Mice |
| title_sort | antagonistic glucagon receptor antibody promotes α cell proliferation and increases β cell mass in diabetic mice |
| url | http://www.sciencedirect.com/science/article/pii/S2589004219301671 |
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