Electronic Thesis and Dissertation Repository

Effect of N-acetyl-L-cysteine prevention or intervention on diet induced beta cell compensation and dysfunction

Madison Wallace, The University of Western Ontario

Abstract

Type 2 diabetes mellitus (T2DM) progression increases oxidative stress which contributes to beta cell compensation and eventual dysfunction. To investigate the role of antioxidant N-acetyl-L-cysteine (NAC) on beta cell function and pancreatic stellate cell activation (aSMA+) during early and late stages of compensation, NAC was used for preventative (p) and intervention (i) treatments in C57BL/6N mice fed a 60% kcal high-fat diet (HFD) for 8 or 22 weeks. Significantly improved glucose tolerance was observed at 22 weeks following pNAC treatment in HFD mice. Although 22-week HFD mice displayed hyperinsulinemia, beta cell hypertrophy, decreased beta cell PDX-1 nuclear localization, and increased intra-islet aSMA+ cells, HFD mice with iNAC treatment normalized beta cell mass and insulin secretion, improved nuclear PDX-1 labeling, and decreased intra- islet aSMA+ staining. In conclusion, NAC treatment prevented beta cell over-compensation associated dysfunction and improved metabolic outcomes in diet-induced obesity T2DM mouse models.