Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.539278
Title: Immune-mediated regulation of glucose uptake in human adipocytes
Author: Brenner, Corinne
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
Availability of Full Text:
Access from EThOS:
Full text unavailable from EThOS. Please try the link below.
Access from Institution:
Abstract:
I have investigated the potential role of Toll-Like Receptors (TLRs) in mediating adipose inflammation in obesity. TLRs are a family of pattern recognition receptors that play a key role in host defence and are also implicated in chronic inflammatory disorders. The finding that TLR4-deficient mice are protected against obesity-induced diabetes led me to hypothesise that TLR expression on adipocytes could play a role in obesity-induced adipose inflammation and metabolic dysfunction. The first chapter investigates the expression and function of TLRs in in vitro differentiated human subcutaneous adipocytes. I found that stimulation with ligands for TLR2, TLR3 and TLR4 but not the other TLRs, induces the expression of pro-inflammatory cytokines. I also explored the use of the TLR adapter molecules MyD88, Mal and TRIF by different TLRs. The second chapter examines whether TLR activation in adipocytes has an effect on glucose uptake. I established a 3H-2-deoxy-D-glucose (2DOG) uptake assay which led to an interesting yet unexpected observation: Stimulation with TLR3 and TLR4 ligands led to a decrease in insulin-stimulated glucose uptake but at the same time, insulin-independent glucose uptake was increased. I showed that these observations are at least partly due to altered expression of different glucose transporter (GLUT) isoforms. As the effects were seen only after prolonged TLR stimulation, I speculated that this was mediated via a secondary secreted factor. The third chapter is based on a cytokine and adipokine array, which I performed to identify cytokines that may be responsible for the effects described in Chapter 2. The secretion of several cytokines/chemokines with diverse pro-inflammatory functions was observed following stimulation with TLR3 and TLR4 ligands. The contribution of some of these factors to altered glucose handling was investigated. Whilst a contribution for ENA-78 was ruled out, I present evidence that IL-1 can contribute to this.
Supervisor: Turner, Jeremy ; Simmonds, Rachel ; Feldmann, Marc Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.539278  DOI: Not available
Share: