Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice
Abstract Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1+ST-HSCs, was a key mechanism for diabetic complications....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-06-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05010-x |
| _version_ | 1797801289688547328 |
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| author | Hideto Kojima Miwako Katagi Junko Okano Yuki Nakae Natsuko Ohashi Kazunori Fujino Itsuko Miyazawa Takahiko Nakagawa |
| author_facet | Hideto Kojima Miwako Katagi Junko Okano Yuki Nakae Natsuko Ohashi Kazunori Fujino Itsuko Miyazawa Takahiko Nakagawa |
| author_sort | Hideto Kojima |
| collection | DOAJ |
| description | Abstract Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1+ST-HSCs, was a key mechanism for diabetic complications. We then hypothesize that those aberrant BMDCs sustainedly impair pancreatic β cells. Here we show that eliminating abnormal BMDCs using bone marrow transplantation results in controlling serum glucose in diabetic mice, in which normoglycemia is sustained even after cessation of insulin therapy. Alternatively, abnormal BMDCs exhibiting epigenetic alterations are treated with an HDAC inhibitor, givinostat, in diabetic mice. As a result, those mice are normoglycemic along with restored insulin secretion even following the cessation of both insulin and givinostat. Diabetic cell fusion between abnormal BMDCs and resident cells is significantly blocked by the combination therapy in the pancreatic islets and thymus while surgical ablation of the thymus completely eliminates therapeutic protection in diabetic mice. In conclusion, diabetes is an epigenetic stem cell disorder with thymic disturbances. The combination may be applied to patients aiming at complete remission from diabetes in clinical medicine. |
| first_indexed | 2024-03-13T04:48:12Z |
| format | Article |
| id | doaj.art-23671901db2d4547b23779f640d86201 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-13T04:48:12Z |
| publishDate | 2023-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-23671901db2d4547b23779f640d862012023-06-18T11:22:22ZengNature PortfolioCommunications Biology2399-36422023-06-016111110.1038/s42003-023-05010-xComplete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin miceHideto Kojima0Miwako Katagi1Junko Okano2Yuki Nakae3Natsuko Ohashi4Kazunori Fujino5Itsuko Miyazawa6Takahiko Nakagawa7Department of Biocommunication Development, Shiga University of Medical ScienceDepartment of Biocommunication Development, Shiga University of Medical ScienceDepartment of Plastic and Reconstructive Surgery, Shiga University of Medical ScienceDepartment of Regenerative Medicine Development, Shiga University of Medical ScienceDepartment of Medicine, Division of Diabetology, Endocrinology and Nephrology, Shiga University of Medical ScienceDepartment of Critical and Intensive Care Medicine, Shiga University of Medical ScienceDepartment of Education Center for Medicine and Nursing, Shiga University of Medical ScienceDepartment of Biocommunication Development, Shiga University of Medical ScienceAbstract Despite the growing epidemic worldwide, diabetes is an incurable disease. We have been focusing on why diabetes manifests refractoriness to any therapy. We recently found that abnormal bone marrow-derived cells (BMDCs), namely, Vcam-1+ST-HSCs, was a key mechanism for diabetic complications. We then hypothesize that those aberrant BMDCs sustainedly impair pancreatic β cells. Here we show that eliminating abnormal BMDCs using bone marrow transplantation results in controlling serum glucose in diabetic mice, in which normoglycemia is sustained even after cessation of insulin therapy. Alternatively, abnormal BMDCs exhibiting epigenetic alterations are treated with an HDAC inhibitor, givinostat, in diabetic mice. As a result, those mice are normoglycemic along with restored insulin secretion even following the cessation of both insulin and givinostat. Diabetic cell fusion between abnormal BMDCs and resident cells is significantly blocked by the combination therapy in the pancreatic islets and thymus while surgical ablation of the thymus completely eliminates therapeutic protection in diabetic mice. In conclusion, diabetes is an epigenetic stem cell disorder with thymic disturbances. The combination may be applied to patients aiming at complete remission from diabetes in clinical medicine.https://doi.org/10.1038/s42003-023-05010-x |
| spellingShingle | Hideto Kojima Miwako Katagi Junko Okano Yuki Nakae Natsuko Ohashi Kazunori Fujino Itsuko Miyazawa Takahiko Nakagawa Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice Communications Biology |
| title | Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice |
| title_full | Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice |
| title_fullStr | Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice |
| title_full_unstemmed | Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice |
| title_short | Complete remission of diabetes with a transient HDAC inhibitor and insulin in streptozotocin mice |
| title_sort | complete remission of diabetes with a transient hdac inhibitor and insulin in streptozotocin mice |
| url | https://doi.org/10.1038/s42003-023-05010-x |
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