PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes
The Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPPs) are novel therapeutic targets for the restoration of β-cell survival and function in diabetes. Their upregulation and activation in β-cells under conditions of both type 1 and type 2 diabetes directly correlates with β-...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2022-02-01
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| Series: | Cell Death Discovery |
| Online Access: | https://doi.org/10.1038/s41420-022-00853-5 |
| _version_ | 1828890819777527808 |
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| author | Blaz Lupse Nick Heise Kathrin Maedler Amin Ardestani |
| author_facet | Blaz Lupse Nick Heise Kathrin Maedler Amin Ardestani |
| author_sort | Blaz Lupse |
| collection | DOAJ |
| description | The Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPPs) are novel therapeutic targets for the restoration of β-cell survival and function in diabetes. Their upregulation and activation in β-cells under conditions of both type 1 and type 2 diabetes directly correlates with β-cell failure; β-cell death and loss of insulin secretory function through disturbance of cell survival control mechanisms. PHLPPs directly dephosphorylate and regulate activities of β-cell survival-dependent kinases AKT and MST1 constituting a regulatory triangle loop to control β-cell apoptosis. PHLPP1 deletion in severely diabetic leptin receptor-deficient db/db mice restored normoglycemia and β-cell area through increased β-cell proliferation and reduced β-cell apoptosis. The beneficial effects of PHLPP1 deficiency in a severe mouse model of obesity and diabetes make PHLPP a new target for β-cell-directed diabetes therapy. |
| first_indexed | 2024-12-13T13:05:52Z |
| format | Article |
| id | doaj.art-d4618fbeabc448989f2203d49d87aa3e |
| institution | Directory Open Access Journal |
| issn | 2058-7716 |
| language | English |
| last_indexed | 2024-12-13T13:05:52Z |
| publishDate | 2022-02-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death Discovery |
| spelling | doaj.art-d4618fbeabc448989f2203d49d87aa3e2022-12-21T23:44:49ZengNature Publishing GroupCell Death Discovery2058-77162022-02-01811410.1038/s41420-022-00853-5PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetesBlaz Lupse0Nick Heise1Kathrin Maedler2Amin Ardestani3Centre for Biomolecular Interactions Bremen, University of BremenCentre for Biomolecular Interactions Bremen, University of BremenCentre for Biomolecular Interactions Bremen, University of BremenCentre for Biomolecular Interactions Bremen, University of BremenThe Pleckstrin homology domain leucine-rich repeat protein phosphatases (PHLPPs) are novel therapeutic targets for the restoration of β-cell survival and function in diabetes. Their upregulation and activation in β-cells under conditions of both type 1 and type 2 diabetes directly correlates with β-cell failure; β-cell death and loss of insulin secretory function through disturbance of cell survival control mechanisms. PHLPPs directly dephosphorylate and regulate activities of β-cell survival-dependent kinases AKT and MST1 constituting a regulatory triangle loop to control β-cell apoptosis. PHLPP1 deletion in severely diabetic leptin receptor-deficient db/db mice restored normoglycemia and β-cell area through increased β-cell proliferation and reduced β-cell apoptosis. The beneficial effects of PHLPP1 deficiency in a severe mouse model of obesity and diabetes make PHLPP a new target for β-cell-directed diabetes therapy.https://doi.org/10.1038/s41420-022-00853-5 |
| spellingShingle | Blaz Lupse Nick Heise Kathrin Maedler Amin Ardestani PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes Cell Death Discovery |
| title | PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes |
| title_full | PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes |
| title_fullStr | PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes |
| title_full_unstemmed | PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes |
| title_short | PHLPP1 deletion restores pancreatic β-cell survival and normoglycemia in the db/db mouse model of obesity-associated diabetes |
| title_sort | phlpp1 deletion restores pancreatic β cell survival and normoglycemia in the db db mouse model of obesity associated diabetes |
| url | https://doi.org/10.1038/s41420-022-00853-5 |
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