Full metadata
Title
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
2017
Contributors
- Burkow, Daniel Harrison (Author)
- Li, Jiaxu (Thesis advisor)
- Castillo-Chavez, Carlos (Thesis advisor)
- Kuang, Yang (Committee member)
- Holechek, Susan (Committee member)
- Arizona State University (Publisher)
Topical Subject
Resource Type
Extent
110 pages
Language
eng
Copyright Statement
In Copyright
Primary Member of
Peer-reviewed
No
Open Access
No
Handle
https://hdl.handle.net/2286/R.I.46258
Level of coding
minimal
Note
Doctoral Dissertation Applied Mathematics for the Life and Social Sciences 2017
System Created
- 2018-02-01 07:04:32
System Modified
- 2021-08-26 09:47:01
- 3 years 2 months ago
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