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Adiponectin and immune tolerance in type 1 diabetes

Pang, Terence Tat Lun (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Type 1 diabetes (T1D) is characterised by pancreatic cell autoimmunity and inflammation, resulting in cell islet destruction and insulin deficiency. Prospective studies from different continents have shown that insulin resistance is independently associated with risk for the development of T1D. We wanted to investigate the role of adiponectin in mediating this link. Adiponectin is a circulating adipokine whose anti-inflammatory and insulin sensitising actions appear to be mediated via two related receptors, AdipoR1 and AdipoR2. We began by characterising adiponectin receptor expression on PBMC by flow cytometry. We showed that monocytes express both receptors abundantly, that this expression correlates with insulin sensitivity in both health and diabetes. Furthermore, expression can be increased with lifestyle intervention. Adiponectin receptor expression on monocytes is reduced in T1D, and we demonstrate this leads to an apparent resistance in the ability of adiponectin to inhibit the stimulatory capacity of antigen presenting cells (APC). Specifically, we show that adiponectin inhibits the stimulatory capacity of APCs through down-regulation of CD86 expression, and that this effect is decreased in T1D. In this way, the release from the regulatory effects of adiponectin is one potential mechanism by which immune tolerance is lost in T1D.

Type of Work:Ph.D. thesis.
Supervisor(s):Narendran, Parth
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical & Experimental Medicine
Subjects:R Medicine (General)
RB Pathology
Institution:University of Birmingham
ID Code:1762
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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