Hormone release from the gastrointestinal tract: mechanisms underlying bile acid-induced GLP-1 release and characterisation of somatostatin signalling. (360G-Wellcome-099825_Z_12_A)

£18,565

Gut hormones are key to the regulation of nutrient homeostasis and therefore particularly relevant to type-2 diabetes. This proposal involves determining the mechanisms underlying secretion of two gut hormones, glucagon-like peptide1 (GLP-1) and somatostatin (SST). GLP-1 is an incretin hormone released in response to components in the intestinal lumen and acts to support nutrient disposal throughout the body. A preliminary project recently identified a G-protein coupled bile acid receptor(GPBA)-independent signalling pathway of bile acid-induced GLP-1 secretion in the distal small intestine. This study proposes to characterise this pathway and determine the roles of apical sodium-dependent bile acid transporter (ASBT) and farsenoid X receptor (FXR) in vitro and in vivo using appropriate inhibitors/agonists and knockout mice. An investigation into the relatively poorly understood inhibitory gut hormone SST is also proposed. SST negatively regulates the secretion of many hormones including GLP-1 but the stimuli and signalling pathways by which SST release occurs are poorly characterised. This proposal involves in vitro assessment ofSST secretion in response to various nutrients and pharmacological tools as well as the relationship between SST and other gut hormones. These data, together with transcriptomics of SST-producing cells, will be used to identifycell-specific signalling pathways.

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Grant Details

Amount Awarded 18565
Applicant Surname Brighton
Approval Committee PhD Studentships
Award Date 2014-01-17T00:00:00+00:00
Financial Year 2013/14
Grant Programme: Title PhD Studentship (Basic)
Internal ID 099825/Z/12/A
Lead Applicant Ms Cheryl Brighton
Partnership Value 18565
Planned Dates: End Date 2016-09-30T00:00:00+00:00
Planned Dates: Start Date 2013-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Sir Stephen O'Rahilly