Inflammatory mechanisms in diabetes: lessons from the beta-cell.

Published

Journal Article (Review)

Inflammation plays an important role in the destruction of pancreatic islet beta-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)-1 beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma. Our laboratory has developed several strategies for protecting beta-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-1 beta+IFN-gamma. 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.

Full Text

Duke Authors

Cited Authors

  • Hohmeier, HE; Tran, VV; Chen, G; Gasa, R; Newgard, CB

Published Date

  • December 2003

Published In

  • Int J Obes Relat Metab Disord

Volume / Issue

  • 27 Suppl 3 /

Start / End Page

  • S12 - S16

PubMed ID

  • 14704737

Pubmed Central ID

  • 14704737

Digital Object Identifier (DOI)

  • 10.1038/sj.ijo.0802493

Language

  • eng

Conference Location

  • England