NIH R01 · 2025
Biochemical Mechanism of Beta-Cell Destruction
Project Summary/Abstract Autoimmune diabetes is characterized by an inflammatory reaction in and around pancreatic islets that is followed by the selective destruction of insulin producing β-cells. The conventional wisdom suggests that cytokines, released during islet inflammation, contribute to the development of autoimmune diabetes by directly impairing b-cell function and reducing β-cell mass. In support of this hypothesis, treatment of islets with IL-1 alone, or in combination with IFN-g and/or TNF, results in an inhibition of insulin secretion and oxidative metabolism, induction of DNA damage and a loss of β-cell viability that is mediated by iNOS expression and the production of…
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