β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia
Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2011-01-01
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| Series: | International Journal of Endocrinology |
| Online Access: | http://dx.doi.org/10.1155/2011/401258 |
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| _version_ | 1832561800964472832 |
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| author | Kristoffer L. Egerod Chunyu Jin Pia Steen Petersen Nils Wierup Frank Sundler Birgitte Holst Thue W. Schwartz |
| author_facet | Kristoffer L. Egerod Chunyu Jin Pia Steen Petersen Nils Wierup Frank Sundler Birgitte Holst Thue W. Schwartz |
| author_sort | Kristoffer L. Egerod |
| collection | DOAJ |
| description | Mice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the β cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the β-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin-treated animals. It is concluded that GPR39 functions in a β-cell protective manner and it is suggested that it is involved in some of the beneficial, β-cell protective effects observed for Zn++ and that GPR39 may be a target for antidiabetic drug intervention. |
| format | Article |
| id | doaj-art-d147df460811438080b301bd70c244b7 |
| institution | Kabale University |
| issn | 1687-8337 1687-8345 |
| language | English |
| publishDate | 2011-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Endocrinology |
| spelling | doaj-art-d147df460811438080b301bd70c244b72025-02-03T01:24:13ZengWileyInternational Journal of Endocrinology1687-83371687-83452011-01-01201110.1155/2011/401258401258β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced HyperglycemiaKristoffer L. Egerod0Chunyu Jin1Pia Steen Petersen2Nils Wierup3Frank Sundler4Birgitte Holst5Thue W. Schwartz6Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkLaboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkLaboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkDivision of Diabetes, Metabolism, and Endocrinology, Department of Experimental Medical Science, Lund University, Lund, SwedenDivision of Diabetes, Metabolism, and Endocrinology, Department of Experimental Medical Science, Lund University, Lund, SwedenLaboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkLaboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, DenmarkMice deficient in the zinc-sensor GPR39, which has been demonstrated to protect cells against endoplasmatic stress and cell death in vitro, display moderate glucose intolerance and impaired glucose-induced insulin secretion. Here, we use the Tet-On system under the control of the proinsulin promoter to selectively overexpress GPR39 in the β cells in a double transgenic mouse strain and challenge them with multiple low doses of streptozotocin, which in the wild-type littermates leads to a gradual increase in nonfasting glucose levels and glucose intolerance observed during both food intake and OGTT. Although the overexpression of the constitutively active GPR39 receptor in animals not treated with streptozotocin appeared by itself to impair the glucose tolerance slightly and to decrease the β-cell mass, it nevertheless totally protected against the gradual hyperglycemia in the steptozotocin-treated animals. It is concluded that GPR39 functions in a β-cell protective manner and it is suggested that it is involved in some of the beneficial, β-cell protective effects observed for Zn++ and that GPR39 may be a target for antidiabetic drug intervention.http://dx.doi.org/10.1155/2011/401258 |
| spellingShingle | Kristoffer L. Egerod Chunyu Jin Pia Steen Petersen Nils Wierup Frank Sundler Birgitte Holst Thue W. Schwartz β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia International Journal of Endocrinology |
| title | β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia |
| title_full | β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia |
| title_fullStr | β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia |
| title_full_unstemmed | β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia |
| title_short | β-Cell Specific Overexpression of GPR39 Protects against Streptozotocin-Induced Hyperglycemia |
| title_sort | β cell specific overexpression of gpr39 protects against streptozotocin induced hyperglycemia |
| url | http://dx.doi.org/10.1155/2011/401258 |
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