Doctoral Dissertations
Date of Award
12-2025
Degree Type
Dissertation
Degree Name
Doctor of Philosophy
Major
Nutritional Sciences
Major Professor
Ahmed Bettaieb
Committee Members
Brynn H. Voy, Mark Hedrick, Paul Dalhaimer
Abstract
Hearing loss is one of the most prevalent impairments globally with rates only set to increase in the coming decades. Hearing loss, as a result of cochlear hair cell death in the inner ear, can be induced by excessive noise, pharmaceuticals, metabolic dysfunction, and age. Primarily, these insults cause upregulation of inflammation, reactive oxygen species generation, and the ER stress response, which induce apoptosis. A wide-array of phytochemicals are shown to alleviate these stress pathways protecting cochlear hair cells from death. Additionally, diabetes-related hearing loss may be due to insulin resistance in cochlear hair cells causing vulnerability to exogenous insult. We set out to characterize ginsenoside-Rc from Panax ginseng as a novel therapeutic to attenuate cochlear hair cell injury and determine its effects in modulating the insulin signaling pathway under diabetic stresses. UB/OC-2 cochlear hair cells were used to interrogate the effects of ginsenoside-Rc in the face of palmitate-induced cellular stress. Efficacy was determined by multi-layered analysis of protein and gene expression as well as monitoring phenotypic changes. Insulin receptor expression in UB/OC-2 cells was genetically decreased and wild-type cells were incubated in gluco- and lipotoxic conditions to model in vivo effects of diabetes mellitus. The effects of ginsenoside-Rc are mediated by its ability to relieve oxidative stress that attenuates the activation of inflammation and the ER stress response. We report the novel characterization of the insulin signaling pathway in cochlear hair cells, which is inhibited by exposure to a hyperglycemic, hyperlipidemic environment. Loss of function of the insulin signaling pathway causes a lower tolerance to stress-induced injury and the effect is rescued by treatment with a physiologically relevant dose of ginsenoside-Rc. Ginsenoside-Rc represents a potential therapeutic option for the prevention of diabetes-related hearing loss by reducing oxidative stress and protecting the insulin signaling pathway. Further research should advance the understanding of the insulin signaling pathway in cochlear hair cells and include investigation of any non-canonical effects.
Recommended Citation
Gill, Nicholas, "Investigating Ginsenoside-Rc's Antidiabetic and Otoprotective Effects in a Novel Model of Diabetes-Induced Hearing Loss. " PhD diss., University of Tennessee, 2025.
https://trace.tennessee.edu/utk_graddiss/13565