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The impact of glucocorticoids upon the insulin sensitivity of skeletal muscle

Morgan, Stuart Andrew (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Glucocorticoid (GC) excess is characterised by central obesity, hypertension, proximal myopathy, insulin resistance and in some cases overt type 2 diabetes (T2D). However, the precise molecular mechanisms responsible for these observation have not been defined in detail. We have shown that GCs reduce the insulin sensitivity of skeletal muscle by impacting upon the insulin signalling cascade at several critical points: IRS1, PI3K and AS160. Furthermore, we have described a novel role of GC, and GCs with insulin, in the regulation of intramyocellular lipid metabolism, which may underpin GC-induced insulin resistance in this tissue. We have also highlighted the importance of 11\(\beta\)-hydroxysteroid dehydrogenase type 1 (11\(\beta\)-HSD1), which controls local GC availability, as a critical regulator of skeletal muscle insulin sensitivity, and have provided new insight into the insulin sensitizing actions of selective 11\(\beta\)-HSD1 inhibitors. In summary, these data highlight the importance of GCs, and pre-receptor GC metabolism in the regulation of lipid metabolic pathways and response to insulin stimulation in skeletal muscle.

Type of Work:Ph.D. thesis.
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Clinical and Experimental Medicine
Subjects:RC Internal medicine
QP Physiology
Institution:University of Birmingham
ID Code:1208
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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