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Access Type
WSU Access
Date of Award
January 2022
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Biomedical Engineering
First Advisor
Ulrike Klueh
Abstract
Significant progress has been made in insulin technology over the past two decades. Continuous Subcutaneous Insulin Infusion (CSII) has enabled improved glycemic control resulting in a reduction and/or a delay in the onset and progression of diabetic complications as compared to conventional injection. Notwithstanding these clinical benefits and the ubiquitous usage of insulin administration, insulin dependent diabetic patients often fail to achieve optimal postprandial glucose control. Currently, CSII is only FDA approved for 3 days and often fails prematurely. One of the limitations is a lack of understanding of the specific mechanisms underlying CSII device failures.
It is widely accepted that people with diabetes experience suboptimal wound healing and have shown an increase in MC degranulation. Nevertheless, the role of MC in diabetes is poorly understood. Our data has proven that insulin phenolic preservatives (IPP) found in the commercial insulin formulations used in CSII are cell and tissue toxic. Furthermore, IPP lead to the activation of skin mast cells which play a direct role in inflammation and fibrosis. Therefore, we hypothesize that commercial IPP are toxic to MC and induce concentration dependent MC activation and cell death which results in acute inflammation followed by chronic inflammation and fibrosis. We propose investigating the specific role of MC in IPP-induced inflammation by using both in vitro and in vivo methods, including two MC cell lines and two MC deficient mouse strains. Furthermore, we propose the development of a filtration membrane for CSII that may eliminate the effects of MC activation during CSII.
Recommended Citation
Kesserwan, Shereen, "Role Of Skin Mast Cells In The Usable Lifespan Of Continuous Subcutaneous Insulin Infusion" (2022). Wayne State University Dissertations. 3736.
https://digitalcommons.wayne.edu/oa_dissertations/3736