title: Inflammatory mechanisms in diabetes: lessons from the beta-cell.
abstract: 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.
authors.affiliation: Sarah W. Stedman Nutrition and Metabolism Center, Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: H E
authors.initials: HE
authors.lastname: Hohmeier
authors.forename: V V
authors.initials: VV
authors.lastname: Tran
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Gasa
authors.forename: C B
authors.initials: CB
authors.lastname: Newgard
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000473:pathology*; D006801:Humans; D007340:Insulinoma / Q000473:pathology*; D007515:Islets of Langerhans / Q000187:drug effects / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
chemical_list: D016207:Cytokines