Presenter: Jordan Davis
Authors: Jordan Davis, Kacie Russon
Faculty Advisor: Jeffery Tessem
Institution: Brigham Young University
Gut-derived metabolitetrimethylamine N-oxide (TMAO) has been commonly associated with chronic illnesses such as cardiovascular disease (CVD) and diabetes caused by obesity.Endoplasmic Reticulum (ER) stress in β-cells caused by high glucose and fatty acid exposure is a major contributor to the development of type 2 diabetes. Studies have shown the beneficial role that TMAO plays in metabolic processes. Our recent research shows that TMAO restores insulin secretion in glucolipotoxic (GLT) conditions and reduces ER stress through the unfolded protein response (UPR) pathway. In GLT conditions, TMAO restored the protein content of UPR receptor IRE1α. IRE1α has been associated to the refolding of proinsulin during ER stress. It remains to be determined how TMAO affects the UPR receptorIRE1α, ER chaperone proteins, and the relationship betweenIRE1α and insulin secretion.We hypothesize that TMAO altersIRE1α in GLT conditions by directly binding to the protein, TMAO upregulates the expression of ER chaperone proteins through IRE1α, and thatIRE1α interaction with TMAO is directly involved in insulin secretion. This project will determine the mechanism by which TMAO protection against GLT occurs inβ-cells, furthering our understanding of metabolites in the body.