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Pathways Regulating Intramyocellular Insulin Sensitivity and Metabolism in Health and Disease

Objective

Currently, there is an urgent need to understand the pathogenesis underpinning insulin resistance (IR) and type 2 diabetes (T2DM), due to their dramatically increasing prevalence. Glucocorticoids (GCs) are potent modulators of skeletal (Sk) muscle insulin sensitivity, as exemplified in patients with GC excess, Cushing’s syndrome, who develop IR and T2DM. Importantly, increased GC generation locally in muscle may contribute to the phenotype in T2DM patients. Although the precise molecular mechanisms driving IR in both T2DM and Cushing’s syndrome are unclear, dysregulated lipid metabolism is a common feature of insulin resistant muscle. This proposal aims to identify how GCs regulate intramyocellular lipid metabolism, and how this impacts on muscle insulin sensitivity. In addition, we will test a novel therapeutic target involved in mediating the metabolic actions of GCs, recently described by Dr Carolyn Cummins, the supervisor of the outgoing phase of this proposal. The complementary expertise in integrative molecular physiology of Dr Cummins, and of the Experienced Researcher, Dr Stuart Morgan, dovetail nicely within an established multi-disciplinary collaborative network of pharmacologists, molecular biologists and analytical chemists at the University of Toronto that have a unifying goal to uncover novel mechanisms regulating IR. Specifically, this proposal employs a systems approach by integrating both in vivo and in vitro pharmacological and genetic manipulation, with lipidomic/proteomic profiling and in-depth molecular characterisations. This novel strategy will significantly advance our understanding of key processes regulating insulin sensitivity in Sk muscle, a process essential for normal glucose homeostasis.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF-GF - Global Fellowships

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2014

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Coordinator

THE UNIVERSITY OF BIRMINGHAM
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 255 349,80
Address
Edgbaston
B15 2TT Birmingham
United Kingdom

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Region
West Midlands (England) West Midlands Birmingham
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 255 349,80

Partners (1)

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