Increased beta cell mass in mice where FGFR1c is expressed in alpha cells
(English)Manuscript (preprint) (Other academic)
FGFR1 is selectively expressed in adult b- but not a-cells and signalling via FGFR1 is crucial for adult b-cell function. When signalling via the FGFR1c pathway is perturbed in b-cells of genetically modified “FRID1” mice, they develop late-onset diabetes and, remarkably, exhibit the three major b-cell defects observed in human type 2 diabetics; i) Impaired glucose sensing due to perturbed b-cell expression of Glut2; ii) increased proinsulin content in b-cells due to drastically reduced production of PC1/3; the enzyme essential for the generation of mature, biologically active insulin from its precursor form, proinsulin; iii) a reduced number of b-cells, as compared with matched controls, due to reduced ability of b-cells to divide after birth. Furthermore, the transcription factor IPF1/PDX1, which controls several key functional properties of b-cells and is linked to diabetes in man, is required to maintain FGF-signalling in b-cells. Together these results point to a crucial role for FGFR1-signalling in controlling the generation of normal numbers of b-cells and glucose homeostasis. To further investigate the mechanism by which FGFR1 signalling influences key b-cell properties as well as b-mass we mis-expressed of FGFR1c in a-cells using the glucagon promoter.
diabetes pancreas fgf
Research subject Developmental Neurosciences
IdentifiersURN: urn:nbn:se:umu:diva-25794OAI: oai:DiVA.org:umu-25794DiVA: diva2:233892
ProjectsIn vivo and in vitro approaches to induce beta cells from stem and progenitor cells