Authors: Eden Beazer, Aubree Bench, Ethan Jones, Jared Carter
Mentors: Jeffrey Tessem
Insitution: Brigham Young University
Incidence of diabetes worldwide has grown from 108 million people in 1980 to 422 million people in 2014, nearly tripling in just thirty-four years. Type 2 diabetes (T2D) is characterized by the loss of pancreatic beta cell mass and the failure of the remaining beta cells to provide adequate insulin. Contributing to the development of T2D is glucolipotoxicity (GLT), a condition characterized by the harmful elevation of glucose and fatty acid levels within beta cells. While there are existing treatments for symptoms of diabetes, much remains to be understood about its underlying causes and effective preventative measures. Flavonoids are naturally occurring phenolic compounds found in many fruits and vegetables that have various anti-inflammatory health benefits. Previous studies suggest that epicatechin, a flavonoid present in cocoa, can reduce the effects of diabetes by diminishing insulin desensitization and increasing glucose stimulated insulin secretion (GSIS). Interestingly, the bioavailability of epicatechin is poor, while its metabolites are more easily absorbed in the small intestine. Further studies demonstrated that under non-stressed conditions in beta-cells, hippuric acid, homovanillic acid, and 5-phenylvaleric acid, metabolites of epicatechin, stimulate insulin secretion at concentrations more realistically found in the body. However, the effects of these metabolites in glucolipotoxic conditions are unknown. Here, we present the effects of epicatechin and its metabolites hippuric acid, homovanillic acid, and 5-phenylvaleric acid on beta cell insulin secretion and mitochondrial respiration under GLT culture conditions. This study aimed to contribute to the limited body of knowledge on the bioactivity of flavonoid metabolites on beta cell function under damaging conditions observed with T2D, offering crucial insights for developing effective strategies to harness the health benefits associated with flavonoids.