Lineage tracing of beta- to α- cell transformation in diabetes: significance and effect of therapeutic drugs
Description: Recent observations suggest that β-cells do not simply survive, proliferate or die but they may also transform into α-cell phenotype. This cellular plasticity may contribute to islet pathogenesis in diabetes by decreasing β- cell mass and increasing numbers of α-cells. We now wish to examine β- to α-cell transition in pathogenesis of diabetes and evaluate the possibility of preventing or reversing this process by incretin receptor activation or DPPIV inhibition. Possible promotion of α- to β-cell transformation by SGLT2 inhibitors will also be explored. Ins1CreRosa26eYFP mice developed for cell lineage tracing with YFP labelled β-cells will be used. Control mice together with mice maintained on high fat diet to induce diabetes used to examine β-cell transformation to α-and other cell phenotypes based on insulin, glucagon, GLP-1 or other islet peptide staining and co-expression of endogenous eYFP immunofluorescence. Changes in islet morphology, together with numbers of Ki67 or tunel positive cells as indicators of β-and α-cell proliferation or apoptosis will also be evaluated. We will examine the effects of SGLT2 inhibition and activation of islet GLP-1 receptors by stable incretin mimetics or a DPPIV inhibitor on β-cell transformation, α-cell numbers and cellular plasticity in the context of their anti-diabetic therapeutic actions.
Funder: Diabetes UK
Amount: £14,740
Funding type: research
Funder scheme: Early-Career Small Grants for Basic Scientists
Start date: 2017-01-02
End date: 2018-01-01
Investigators: Charlotte Moffett, Charlotte Moffett
Institution: University of Ulster
Funded outputs count: 0
Funder award ID: 16/0005511
OpenAlex ID: G9000417698