Gene therapy for diabetes: strategies for β-cell modification and replacement

Levine, Fred

doi:10.1002/(sici)1099-0895(199712)13:4<209::aid-dmr198>3.3.co;2-e

Cited by 13 publications

(22 citation statements)

References 185 publications

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“…Our data, as well as work by Kolodka et al, 28 have shown that secretion of insulin not only restored BG levels to normal, or close to normal but also prevented development of ketoacidosis. 47,54 CD-1 nude mice, which received AdCMVhInsM vector and were challenged with intraperitoneal injection of glucose solution, developed glucose tolerance compared with streptozotocin-treated diabetic control mice. This was confirmed by prolonged survival of these animals compared with the animals that received AdCMVhInsWT or controls.…”

Section: Discussionmentioning

confidence: 99%

“…Glucose-regulated gene transcription is possible by using phosphoenolpyruvate carboxykinase (PEPCK) promoter or the L-type pyruvate kinase (L-PK) promoter inserted above insulin gene sequence. The PEPCK promoter is stimulated by glucagon and inhibited by insulin, 8,23,47,63,64 while the L-PK promoter is triggered by glucose and fructose and inhibited by glucagon. 10,23,24,27,47,65 Glucose-stimulated insulin release was studied using glucokinase and GLUT2 promoters.…”

Section: Discussionmentioning

confidence: 99%

“…Glucokinase promoter is stimulated by insulin and inhibited by glucagon. 6,23,47,54,66,68 GLUT2 has a glucose-sensitive effect on insulin secretion but not in the physiological range. 4,23,47,54,66,67 Pancreatic acinar cells have single-channel currents from the baso-lateral surface of pancreatic acini.…”

Section: Discussionmentioning

confidence: 99%

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Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

Shifrin

Auricchio

et al. 2001

Gene Ther

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

Shifrin

Auricchio

et al. 2001

Gene Ther

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“…We and others have therefore been investigating the potential utility of engineered cell lines as surrogates for primary islet cells in the treatment of type I diabetes. [11][12][13][14][15] We envision that such cells would be delivered in the context of a macroencapsulation device that will prevent contact of cellular elements of the immune system and the engrafted tissue. 12 However, immunoisolation barriers will not protect the cells from damage caused by soluble inflammatory mediators such as cytokines and ROS/RNS.…”

Section: Development Of Methods For Protecting Insulinoma Cell Lines mentioning

confidence: 99%

Inflammatory mechanisms in diabetes: lessons from the β-cell

et al. 2003

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Inflammation plays an important role in the destruction of pancreatic islet b-cells that leads to type I diabetes. This involves infiltration of T-cells and macrophages into the islets and local production of inflammatory cytokines such as interleukin (IL)-1b, tumor necrosis factor (TNF)-a, and interferon (IFN)-g. Our laboratory has developed several strategies for protecting b-cells against oxidative stress and cytokine-induced cytotoxicity. These include a cytokine selection strategy that results in cell lines that are resistant to the combined effects of IL-1b þ IFN-g. More recently, we have combined the cytokine selection procedure with overexpression of the antiapoptotic gene bcl-2, resulting in cell lines with greater resistance to oxidative stress and cytokine-induced damage than achieved with either procedure alone. This article summarizes this work and the remarkably divergent mechanisms by which protection is achieved in the different model systems. We also discuss the potential relevance of insights gained from these approaches for enhancing islet cell survival and function in both major forms of diabetes.

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“…Via this process, it is possible to insert [116], remove [117], modify [118] or silence [119] defective genes, thus treating even genetically inherited disease. The most studied nanocarriers for the gene delivery include viral particles [120], liposomes [121] and polymers [122].…”

Section: Apoferritin In Gene Deliverymentioning

confidence: 99%