Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice
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| Title: | Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice |
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| Authors: | Burkhardt, Brant R.1 burkhardtb@email.chop.edu, Parker, Mathew J.1, Zhang, Y. Clare1, Song, Sihong2, Wasserfall, Clive H.1,3, Atkinson, Mark A.1,3 |
| Source: | FEBS Letters. Oct2005, Vol. 579 Issue 25, p5759-5764. 6p. |
| Subjects: | Hypoglycemic agents, Pancreatic secretions, Blood plasma, Hormones |
| Abstract: | Abstract: Insulin production afforded by hepatic gene therapy (HGT) retains promise as a potential treatment for type 1 diabetes, but successful approaches have been limited. We employed a novel and previously untested promoter for this purpose, glucose transporter-2 (GLUT2) to drive insulin production via delivery by recombinant adeno-associated virus (rAAV). In vitro, the GLUT2 promoter was capable of robust glucose-responsive expression in transduced HepG2 human hepatoma cells. Therefore, rAAV constructs were designed to express the furin-cleavable human preproinsulin B10 gene, under the control of the murine GLUT2 promoter and packaged for delivery with rAAV expressing the type 5 capsid. Streptozotocin-induced diabetic mice were subjected to hepatic portal vein injection immediately followed by implantation of a sustained-release insulin pellet to allow time for transgenic expression. All mice injected with the rAAV5-GLUT2-fHPIB10 virus remained euglycemic for up to 35 days post-injection, with 50% euglycemic after 77 days post-injection. In contrast, mock-injected mice became hyperglycemic within 15 days post-injection following dissolution of the insulin pellet. Serum levels of both human insulin and C-peptide further confirmed successful transgenic delivery by the rAAV5-GLUT2-fHPIB10 virus. These findings indicate that the GLUT2 promoter may be a potential candidate for regulating transgenic insulin production for hepatic insulin gene therapy in the treatment of type I diabetes. [Copyright &y& Elsevier] |
| Copyright of FEBS Letters is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Engineering Source |
| FullText | Text: Availability: 0 |
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| Header | DbId: egs DbLabel: Engineering Source An: 18782016 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Burkhardt%2C+Brant+R%2E%22">Burkhardt, Brant R.</searchLink><relatesTo>1</relatesTo><i> burkhardtb@email.chop.edu</i><br /><searchLink fieldCode="AR" term="%22Parker%2C+Mathew+J%2E%22">Parker, Mathew J.</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Zhang%2C+Y%2E+Clare%22">Zhang, Y. Clare</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Song%2C+Sihong%22">Song, Sihong</searchLink><relatesTo>2</relatesTo><br /><searchLink fieldCode="AR" term="%22Wasserfall%2C+Clive+H%2E%22">Wasserfall, Clive H.</searchLink><relatesTo>1,3</relatesTo><br /><searchLink fieldCode="AR" term="%22Atkinson%2C+Mark+A%2E%22">Atkinson, Mark A.</searchLink><relatesTo>1,3</relatesTo> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22FEBS+Letters%22">FEBS Letters</searchLink>. Oct2005, Vol. 579 Issue 25, p5759-5764. 6p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Hypoglycemic+agents%22">Hypoglycemic agents</searchLink><br /><searchLink fieldCode="DE" term="%22Pancreatic+secretions%22">Pancreatic secretions</searchLink><br /><searchLink fieldCode="DE" term="%22Blood+plasma%22">Blood plasma</searchLink><br /><searchLink fieldCode="DE" term="%22Hormones%22">Hormones</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Abstract: Insulin production afforded by hepatic gene therapy (HGT) retains promise as a potential treatment for type 1 diabetes, but successful approaches have been limited. We employed a novel and previously untested promoter for this purpose, glucose transporter-2 (GLUT2) to drive insulin production via delivery by recombinant adeno-associated virus (rAAV). In vitro, the GLUT2 promoter was capable of robust glucose-responsive expression in transduced HepG2 human hepatoma cells. Therefore, rAAV constructs were designed to express the furin-cleavable human preproinsulin B10 gene, under the control of the murine GLUT2 promoter and packaged for delivery with rAAV expressing the type 5 capsid. Streptozotocin-induced diabetic mice were subjected to hepatic portal vein injection immediately followed by implantation of a sustained-release insulin pellet to allow time for transgenic expression. All mice injected with the rAAV5-GLUT2-fHPIB10 virus remained euglycemic for up to 35 days post-injection, with 50% euglycemic after 77 days post-injection. In contrast, mock-injected mice became hyperglycemic within 15 days post-injection following dissolution of the insulin pellet. Serum levels of both human insulin and C-peptide further confirmed successful transgenic delivery by the rAAV5-GLUT2-fHPIB10 virus. These findings indicate that the GLUT2 promoter may be a potential candidate for regulating transgenic insulin production for hepatic insulin gene therapy in the treatment of type I diabetes. [Copyright &y& Elsevier] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of FEBS Letters is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1016/j.febslet.2005.09.060 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 6 StartPage: 5759 Subjects: – SubjectFull: Hypoglycemic agents Type: general – SubjectFull: Pancreatic secretions Type: general – SubjectFull: Blood plasma Type: general – SubjectFull: Hormones Type: general Titles: – TitleFull: Glucose transporter-2 (GLUT2) promoter mediated transgenic insulin production reduces hyperglycemia in diabetic mice Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Burkhardt, Brant R. – PersonEntity: Name: NameFull: Parker, Mathew J. – PersonEntity: Name: NameFull: Zhang, Y. Clare – PersonEntity: Name: NameFull: Song, Sihong – PersonEntity: Name: NameFull: Wasserfall, Clive H. – PersonEntity: Name: NameFull: Atkinson, Mark A. IsPartOfRelationships: – BibEntity: Dates: – D: 24 M: 10 Text: Oct2005 Type: published Y: 2005 Identifiers: – Type: issn-print Value: 00145793 Numbering: – Type: volume Value: 579 – Type: issue Value: 25 Titles: – TitleFull: FEBS Letters Type: main |
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