abstract: 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. / Dissertation/Thesis / Doctoral Dissertation Applied Mathematics for the Life and Social Sciences 2017
| Identifer | oai:union.ndltd.org:asu.edu/item:46258 |
| Date | January 2017 |
| Contributors | Burkow, Daniel Harrison (Author), Li, Jiaxu (Advisor), Castillo-Chavez, Carlos (Advisor), Kuang, Yang (Committee member), Holechek, Susan (Committee member), Arizona State University (Publisher) |
| Source Sets | Arizona State University |
| Language | English |
| Detected Language | English |
| Type | Doctoral Dissertation |
| Format | 110 pages |
| Rights | http://rightsstatements.org/vocab/InC/1.0/, All Rights Reserved |
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