Publication Date
2022
Document Type
Thesis
Committee Members
Mauricio Di Fulvio, Ph.D. (Advisor); Courtney Sulentic, Ph.D. (Committee Member); Khalid Elased, Pharm.D., Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Pancreatic islet β-cell plays an essential role in insulin release and hence glucose homeostasis. The maintenance of glucose homeostasis depends on β-cell ability to cope with enough insulin to fulfill metabolic and physiological demands. Adequate insulin release is the result of highly complex and dynamic interplays between acute changes in β- cell electrical activity, exocytosis and chronic adaptations in cellular function, volume, mass and proliferation. All of this appears modulated, to some extent, by the functional presence of Slc12a2 symporters, also known as Na+K+2Cl– cotransporter-1 (Nkcc1), which accumulates intracellular Cl– above its electrochemical equilibrium. Recent studies from our laboratory showed that mice lacking Nkcc1 in β-cell (Nkcc1βKO) develop a cluster of metabolic phenotypes reminiscent of the metabolic syndrome i.e., hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, steatohepatitis and overweight. The present study is aimed at determining the potential relationship between those phenotypes and pancreas morphometric parameters including islet size, β-cell number, volume, mass and neogenesis. The results presented here indicate that elimination of Nkcc1 from β-cell negatively impact those parameters, even before the onset of overweight and its metabolic complications. Therefore, we propose that Nkcc1 plays a potential causative role in the development of metabolic syndrome.
Page Count
93
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2022
Copyright
Copyright 2022, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
ORCID ID
0000-0001-6122-1999
