Authors: Aubree Bench, Eden Beazer, Ethan Jones, Jared Carter
Mentors: Jeff Tessem
Insitution: Brigham Young University
The pathogenesis of both type 1 and type 2 diabetes is associated with progressive beta-cell death and a resultant loss of insulin secretion, making preservation of functional beta-cell mass a priority in the prevention and treatment of diabetes. Type 1 diabetes (T1D) beta-cell death is mediated by autoimmune attack, exposing cells to pro-inflammatory cytokines such as IL-1B, TNF-A and IFN-G. Type 2 diabetes (T2D) beta-cell loss is induced by a destructive metabolic state of persistent hyperglycemia and elevated free fatty acid (FFA) levels. Our lab has previously demonstrated that the monomeric flavonoid epicatechin and its gut bacteria derived metabolites enact diverse beneficial effects on beta-cell viability, including reduction of oxidative stress and increased mitochondrial respiration, both important intermediates in the prevention of cell death. Here we present data testing the ability of epicatechin and its gut bacteria derived metabolites homovanillic acid, hippuric acid, and 5-phenylavaleric acid to protect against cytokine or glucolipotoxic (GLT) mediated beta-cell death. This study’s findings have important implications for differing therapeutic approaches to T1D and T2D, as well as insight into beta-cell death mechanisms and development of interventions by which those specific pathways might be inhibited.