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KMID : 1134220090290020176
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Hanyang Medical Reviews
2009 Volume.29 No. 2 p.176 ~ p.185
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Peptide/Gene Therapy for the Prevention of Diabetes
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Park Yong-Soo
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Abstract
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Pancreatic β cell function deteriorates continuously in type 2 diabetes patients despite optimal treatment, which has been attributed to hyperglycemia itself via formation of excess reactive oxygen species. Studies of animals with spontaneous
autoimmune diabetes have revealed that autoreactive T cells that mediate islet β cell destruction can be manipulated by the administration of cytokines, especially Th2 cytokines. Restoration of self tolerance at certain time period may facilitate
islet cell regeneration and may enable complete recovery from diabetes. To overcome short halflives of cytokines, we would like to deliver genes which enable cytokine production in the body. We also induced antiapoptotic molecules in β cells, the protective effect of which we screened systematically, applying new gene/peptide delivery strategies. In this study, the effect of peptide delivery using specific carriers was evaluated both in vitro and in vivo. In view of the mmunoregulatory activity of Th2 cytokines, we investigated whether systemic or local cytokine gene therapy stops islet
destructive autoimmunity and regenerates β cells of the pancreas in NOD mice. In addition, treatment of β cells with the antioxidant metallothionein resulted in a significant reduction in pathological changes and restored GSIS. Specific inhibition of NF-κB activation by retroviral transduction of dominant negative inhibitor of NF-κB also protected β cells. Therefore, these results suggest the protective influence of these gene/ peptide delivery as an adjunctive measure to clinical islet transplantation may enable us to improve the results of the cell-based treatment to overcome the battle against the debilitating disease of diabetes mellitus
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KEYWORD
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Peptide therapy, Gene therapy, Tat- fusion protein, Slow release growth factor delivery
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