Secretion in 3T3-L1 adipocytes

Clarke, Mairi (2006) Secretion in 3T3-L1 adipocytes. PhD thesis, University of Glasgow.

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Abstract

Adipocytes secrete a range of proteins, called adipokines, with important roles in a variety of biological processes such as metabolism, cardiovascular function and immunity. ACRP30 (also known as adiponectin) is an adipokine that displays anti-diabetic and anti-inflammatory properties and may prevent atherosclerosis. It is secreted exclusively by adipocytes and circulating levels of ACRP30 are reduced in obesity and diabetes. Although this protein has been widely studied, little is known about the mechanisms of secretion of ACRP30 in adipocytes. Here I have examined secretion of ACRP30 in 3T3-L1 adipocytes with the aim of understanding the secretory pathways used by ACRP30 as it traffics to the cell surface. Using intracellular localisation techniques 1 have shown that ACRP30 overlaps with transferrin receptor positive membranes, evidence that ACRP30 traffics via the transferrin- receptor positive endosomal system. This was supported by results showing that ablation of the transferrin-receptor positive endosomes strongly inhibited ACRP30 secretion, I have also investigated the effects of overexpressing mutant forms of the small GTPases Rabl1 and Arf6, Overexpression of Rabl 1 S25N significantly reduced basal and insulin- stimulated ACRP30 secretion and I have demonstrated that Arf6 plays a role in ACRP30 secretion. With the aim of identifying new adipokines, I have conducted a proteomic analysis of the proteins secreted by 3T3-L1 adipocytes. In this study, I identified 25 proteins that had not previously been identified as adipocyte-secreted. In functional studies, two of these proteins, orosomucoid and Nm23 could be shown to affect insulin-stimulated glucose uptake. In monocyte adhesion assays orosomucoid had anti-inflammatory effects.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: Gwyn Gould
Keywords: Molecular biology
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71050
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 10 May 2019 10:49
URI: http://theses.gla.ac.uk/id/eprint/71050

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