Skip to main content

The etiology and natural history of type 2 diabetes

Resource type
Thesis type
(Dissertation) Ph.D.
Date created
2005
Authors/Contributors
Author: Topp, Brian
Abstract
Type 2 diabetes is a complex disorder characterized by progressive defects in nearly every aspect of metabolic regulation. Despite this complexity, traditional in vivo methodologies have limited experimental examination to a small number of metabolic indices at one or two points in time. As a result the etiology and natural history of this disease remain unclear and much debated. This thesis takes a two pronged approach to this problem. First, a mathematical model is developed to incorporate experimental data from different sources into an integrated representation of metabolic regulation. Bifurcation and simulation analysis of this model are used to investigate mechanisms of metabolic regulation as well as the pathogenesis of type 2 diabetes. Second, new experimental methodologies are developed that greatly improve the practicality of estimating several key metabolic indices in vivo. Applying these methodologies to animal models of type 2 diabetes allowed us to perform a fully dynamic and integrative analysis of the pathogenesis of type 2 diabetes in two commonly used animal models. Overall, data from this thesis suggests that the etiology of type 2 diabetes lies in two distinct abnormalities; rapid development of insulin resistance coupled to impaired P-cell mass adaptation.
Document
Copyright statement
Copyright is held by the author.
Permissions
The author has not granted permission for the file to be printed nor for the text to be copied and pasted. If you would like a printable copy of this thesis, please contact summit-permissions@sfu.ca.
Scholarly level
Language
English
Download file Size
etd2069.pdf 1.69 MB

Views & downloads - as of June 2023

Views: 0
Downloads: 0