Erica Graham
Department of Mathematics, NC State University

Title: Mitochondria's Revenge: The Role of Oxidative Stress in Type 2 Diabetes

Abstract: Type 2 diabetes is a worldwide epidemic with many complex mechanisms of 
its long-term pathogenesis.  An imbalance between glucose and insulin are 
characteristic of the disease, wherein insulin-responsive cells are unable to meet 
metabolic demands, termed insulin resistance, and glucose dysregulation ensues.  The 
progression of insulin resistance, which persists for decades, is itself 
incompletely understood, though several mechanisms have been proposed.  We focus on 
feedback between skeletal muscle mitochondria and oxidative stress to explain the 
metabolic dysfunction in insulin resistance.  We utilize deterministic and 
stochastic methods to model long-term intracellular dynamics, and we find that 
overnutrition can indeed generate the oxidative stress-mediated mitochondrial 
defects that, through positive feedback, inhibit normal cellular responses to 
insulin.