Abstract

Since its discovery in 1922, insulin has been the life-saving treatment for type 1 diabetes mellitus. As the disease is caused by the loss of insulin-producing pancreatic islets, transplantation of donor islets has the potential to not only supplement insulin replacement therapy but to cure type 1 diabetes. However, long-term insulin independence (> 2 years post-transplant) remains a challenge partly due to low islet blood flow immediately following transplantation leading to hypoxic stress on islets. The goal of our studies is to improve islet engraftment by monitoring and promoting the regrowth and maturation of new islet blood vessels in a clinically applicable manner. The developed technique is based on intravascular injection of a FDA-approved contrast agent which leaks from and accumulates around permeable immature blood vessels. Rapidly acquired MRI scans following contrast administration can then show the location and extent of new vessel formations. Our studies showed dynamic contrast-enhanced MRI to be successful in determining a timeline for islet revascularization as well as evaluating the effectiveness of a hyperbaric oxygen-based engraftment-enhancing therapy. The results are an important step in advancing islet transplantation as a potential cure for type 1 diabetes.

LLU Discipline

Biochemistry

Department

Basic Sciences

School

School of Medicine

First Advisor

Hathout, Eba

Second Advisor

Duerksen-Hughes, Penelope

Third Advisor

Kirsch, Wolff

Fourth Advisor

Obenaus, Andre

Fifth Advisor

Sowers, Lawrence

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

January 2011

Date (Title Page)

6-1-2011

Language

English

Library of Congress/MESH Subject Headings

Insulin; Type 1 Diabetes Mellitus; Magnetic Resonance Imaging;

Subject - Local

Dynamic Contrast-Enhanced MRI; Pancreatic Islet Transplants

Type

Dissertation

Page Count

90 p.

Digital Format

Application/PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses & Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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