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)
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 |