Intramyocellular Lipids and the Progression of Muscular Insulin Resistance
Description
Diabetes is a disease characterized by reduced insulin action and secretion, leading to elevated blood glucose. In the 1990s, studies showed that intravenous injection of fatty acids led to a sharp negative response in insulin action that subsided hours after the injection. The molecule associated with diminished insulin signalling response was a byproduct of fatty acids, diacylglycerol. This dissertation is focused on the formulation of a model built around the known mechanisms of glucose and fatty acid storage and metabolism within myocytes, as well as downstream effects of diacylglycerol on insulin action. Data from euglycemic-hyperinsulinemic clamp with fatty acid infusion studies are used to validate the qualitative behavior of the model and estimate parameters. The model closely matches clinical data and suggests a new metric to determine quantitative measurements of insulin action downregulation. Analysis and numerical simulation of the long term, piecewise smooth system of ordinary differential equations demonstrates a discontinuous bifurcation implicating nutrient excess as a driver of muscular insulin resistance.
Date Created
The date the item was original created (prior to any relationship with the ASU Digital Repositories.)
2017
Agent
- Author (aut): Burkow, Daniel Harrison
- Thesis advisor (ths): Li, Jiaxu
- Thesis advisor (ths): Castillo-Chavez, Carlos
- Committee member: Kuang, Yang
- Committee member: Holechek, Susan
- Publisher (pbl): Arizona State University