XIAP gene expression Protects β-cells and human islets from apoptotic cell death

Hao Wu, Ravikiran Panakanti, Feng Li, Ram I. Mahato

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Islet transplantation has the potential to treat type I diabetes, however, its clinical application is limited due to the massive apoptotic cell death and other post-transplantation challenges to islet grafts. Therefore, the objective of this study was to determine whether ex vivo transduction of rat insulin producing INS-1E cells and human islets with adenoviral vector encoding human X-linked inhibitor of apoptosis (Adv-hXIAP) can protect them from inflammatory cytokines and improve their viability and function. There was dose dependent XIAP gene expression. XIAP expression led to decrease in the activities of caspase 3/7, 8 and 9, resulting in reduced apoptotic cell death induced by a cocktail of inflammatory cytokines such as IL-1β, TNFα, and IFNγ. Prolonged normoglycemic control could be achieved by transplantation of Adv-XIAP transduced human islets under the kidney capsule of streptozotocin induced diabetic NOD-SCID mice. Immunohistological staining of the islets bearing kidney sections at day 42 after transplantation was positive for insulin. Moreover, the protective effect of XIAP was reversed by coadministration of XIAP inhibitor embelin. These results indicate that ex vivo transduction of islets with Adv-XIAP will decrease cytokine induced apoptosis and improve the outcome of islet transplantation.

Original languageEnglish (US)
Pages (from-to)1655-1666
Number of pages12
JournalMolecular Pharmaceutics
Volume7
Issue number5
DOIs
StatePublished - Oct 4 2010

Fingerprint

Islets of Langerhans
Islets of Langerhans Transplantation
Cell Death
Transplantation
Cytokines
Gene Expression
Insulin
Apoptosis
Caspase 7
Kidney
Inbred NOD Mouse
SCID Mice
Caspase 9
Streptozocin
Type 1 Diabetes Mellitus
Interleukin-1
Caspase 3
Capsules
Staining and Labeling
Transplants

Keywords

  • Human islets
  • XIAP
  • adenoviral vectors
  • apoptosis
  • diabetes
  • islet transplantation

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

XIAP gene expression Protects β-cells and human islets from apoptotic cell death. / Wu, Hao; Panakanti, Ravikiran; Li, Feng; Mahato, Ram I.

In: Molecular Pharmaceutics, Vol. 7, No. 5, 04.10.2010, p. 1655-1666.

Research output: Contribution to journalArticle

Wu, Hao ; Panakanti, Ravikiran ; Li, Feng ; Mahato, Ram I. / XIAP gene expression Protects β-cells and human islets from apoptotic cell death. In: Molecular Pharmaceutics. 2010 ; Vol. 7, No. 5. pp. 1655-1666.
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