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Proteomic and phosphoproteomic analysis of the effect of exendin-4 treatment on the rat pancreatic beta cell line ins-1

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Title: Proteomic and phosphoproteomic analysis of the effect of exendin-4 treatment on the rat pancreatic beta cell line ins-1
Authors: Al Mismar, Rasha
Item Type: Thesis or dissertation
Abstract: Diabetes is a major worldwide health problem, and the incidence is increasing. Although the etiology of types 1 and 2 diabetes is different, the developmental complications of both types involve destruction of pancreatic beta cells. Enhancing or inducing pancreatic beta cell proliferation is thus a focus of much research. Exendin-4, a GLP-1 analogue, was introduced into the clinic in 2005 as an inducer of insulin secretion, but also has proliferative effects on pancreatic beta cells in vitro. These effects have been characterized in targeted studies, identifying specific proteins in particular signaling pathways. In our study, we aimed to carry out global proteomic and phosphoproteomic relative quantitation screening to identify the proteins and their phosphorylation sites regulated by exendin-4 treatment in rat ins-1 cells, compared to their untreated counterparts. We were able to quantify 3766 proteins among which 667 proteins were significantly regulated. In addition, we quantified 2170 phosphosites, 400 of which were significantly regulated. The significantly regulated proteins and phosphosites after exendin-4 treatment pointed to a protective role for this peptide in maintaining cell survival and inhibiting apoptosis due to the stress induced by the serum starvation, which is in agreement of previous reports. This thesis thus provides the first global proteomic analysis of the effects of exendin-4 on the rat pancreatic beta cells. Further studies employing different culture conditions and knockdown or overexpression of candidate proteins are now required to give deeper insight into the pathways involved.
Content Version: Open Access
Issue Date: May-2017
Date Awarded: Sep-2017
URI: http://hdl.handle.net/10044/1/73979
DOI: https://doi.org/10.25560/73979
Supervisor: Murphy, Kevin
Taheri, Shahrad
Department: Department of Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Master of Philosophy (MPhil)
Appears in Collections:Medicine PhD theses



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