Hanyang Med Rev.  2009 May;29(2):176-185.

Peptide/Gene Therapy for the Prevention of Diabetes

Affiliations
  • 1Department of Internal Medicine and Bioengineering, School of Medicine and Engineering, Hanyang University,Seoul, Korea. parkys@hanyang.ac.kr

Abstract

Pancreatic betacell 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 betacell 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 betacells, 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 immunoregulatory activity of Th2 cytokines, we investigated whether systemic or local cytokine gene therapy stops islet destructive autoimmunity and regenerates betacells of the pancreas in NOD mice. In addition, treatment of betacells with the antioxidant metallothionein resulted in a significant reduction in pathological changes and restored GSIS. Specific inhibition of NF-kappaB activation by retroviral transduction of dominant negative inhibitor of NF-kappaB also protected betacells. 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.

Keyword

Peptide therapy; Gene therapy; Tat- fusion protein; Slow release growth factor delivery

MeSH Terms

Animals
Autoimmunity
Cytokines
Diabetes Mellitus
Diabetes Mellitus, Type 1
Genetic Therapy
Humans
Hyperglycemia
Islets of Langerhans
Islets of Langerhans Transplantation
Metallothionein
Mice
Mice, Inbred NOD
NF-kappa B
Pancreas
Reactive Oxygen Species
Regeneration
Self Tolerance
T-Lymphocytes
Zidovudine
Cytokines
Metallothionein
NF-kappa B
Reactive Oxygen Species
Zidovudine
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