Abstract
The β-cells in the pancreatic islets of Langerhans are the targets of autoreactive T-cells and are destroyed in type 1 diabetes. Macrophage-derived interleukin-lβ (IL-1β) is important in eliciting β-cell dysfunction and initiating β-cell damage in response to microenvironmental changes within islets. In particular, IL-1β can impair glucose-stimulated insulin production in β-cells in vitro and can sensitize them to Fas (CD95)/FasL- triggered apoptosis. In this report, we have examined the ability to block the detrimental effects of IL-1β by genetically modifying islets by adenoviral gene transfer to express the IL-1 receptor antagonist protein. We demonstrate that adenoviral gene delivery of the cDNA encoding the interleukin-1 receptor antagonist protein (IL-1Ra) to cultured islets results in protection of human islets in vitro against IL-lβ-induced nitric oxide formation, impairment in glucose-stimulated insulin production, and Fas- triggered apoptosis activation. Our results further support the hypothesis that IL-1β antagonism in in situ may prevent intra-islet proinsulitic inflammatory events and may allow for an in vivo gene therapy strategy to prevent insulitis and the consequent pathogenesis of diabetes.
Original language | English (US) |
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Pages (from-to) | 1730-1736 |
Number of pages | 7 |
Journal | Diabetes |
Volume | 48 |
Issue number | 9 |
DOIs | |
State | Published - 1999 |
Externally published | Yes |