Mechanisms underlying Glucose-dependent Insulinotropic Polypeptide (GIP) secretion and function. (360G-Wellcome-084210_Z_07_Z)

£1,177,494

Modulating glucose-dependent insulinotropic polypeptide (GIP) secretion is a potential strategy for the treatment of diabetes and obesity. However, the cellular mechanisms underlying GIP release from K-cells are poorly characterised because the cells have not, historically, been readily distinguishable from their epithelial neighbours. I recently created transgenic mouse strains expressing a fluorescent marker under the control of the GIP promoter (GIP-Venus mice), enabling, for the first time, the identification and purification of living primary K-cells. These will be characterised by electrophysiology, single cell fluorescence imaging, gene expression analysis and secretion studies, to identify agents and pathways that modulate GIP secretion and that could be targeted to control GIP release in vivo. GIP-Venus mice will be crossed with the Immortomouse to develop K-cell specific lines, which are not currently available but would be a valuable tool for research requiring a higher cell number or longer culture times. Further transgenic mouse strains will be created, expressing the diphtheria toxin receptor under the control of the GIP promoter, enabling conditional K-cell ablation in murine models of obesity. The metabolic consequences of acute and chronic GIP depletion will be investigated in these mice, to evaluate the potential effects of reducing GIP secretion in vivo.

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Grant Details

Amount Awarded 1177494
Applicant Surname Reimann
Approval Committee Basic Science Interview Committee
Award Date 2008-04-09T00:00:00+00:00
Financial Year 2007/08
Grant Programme: Title Senior Research Fellowship Basic
Internal ID 084210/Z/07/Z
Lead Applicant Prof Frank Reimann
Partnership Value 1177494
Planned Dates: End Date 2014-09-30T00:00:00+00:00
Planned Dates: Start Date 2008-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Sir Stephen O'Rahilly