This thesis aims to understand the maturation and functional maintenance of insulin-secreting β-cells in the pancreas. Here in the introduction, I will first present the overall anatomy and physiology of the pancreas, as pancreas construction and islet architecture are both critical contexts of β-cell research. I will then introduce the fundamental mechanism of β-cell function, i.e. glucose-stimulated insulin secretion (GSIS). Herein I will discuss physiological processes involved in the GSIS pipeline, focusing on the Ca2+ signaling-coupled vesicle exocytosis, which is most relevant to my research. After introducing β-cell function, I will present our current understanding of how mature β-cells featuring robust GSIS are formed. Next, I will discuss long-term maintenance of β-cell function and stability during postnatal stages. In particular, I will highlight the various types of cell stress that β-cells are likely to face and the intrinsic key factors required to handle them. To underscore the significance of postnatal β-cell stability, I will present the relationship between β-cell stress and the development of diabetes. In the last part of this introduction, I will focus on the most recent advances that scientists have made in generating β-cells as a restorative cell therapy for the treatment of diabetes, and the major knowledge gap that needs to be addressed in this field. Finally, I will discuss how this thesis research will likely broaden our perspectives of β-cell maturation and functional maintenance and further contribute to generating of long-lived functional β-cells to improve human health.
|Commitee:||Bader, David, Chiang, Chin, Gannon, Maureen, Gu, Guoquiang, Weil, Tony|
|Department:||Cell and Developmental Biology|
|School Location:||United States -- Tennessee|
|Source:||DAI-B 80/06(E), Dissertation Abstracts International|
|Keywords:||Beta-cell, Development, Diabetets, Mouse, Myt factors, Synaptotagmin IV|
Copyright in each Dissertation and Thesis is retained by the author. All Rights Reserved
dissertation or thesis. The supplemental files are provided "AS IS" without warranty. ProQuest is not responsible for the
content, format or impact on the supplemental file(s) on our system. in some cases, the file type may be unknown or
may be a .exe file. We recommend caution as you open such files.
supplemental files is subject to the ProQuest Terms and Conditions of use.