Beta cells intimately interact with endothelial cells for generation and function, during development and adulthood. Transgenic mice that conditionally overexpress the VEGF-A decoy receptor sFLT1 specifically near beta cells, experience islet hypovascularization but no negative effects on beta cell proliferation. We elaborated on this mouse model and discovered that when sFLT1 expression is stopped following blood vessel ablation, the beta cell cycle is activated and its cell mass increased. The current application concentrates on beta cell-autonomous processes and on the cells the newly- formed beta cells may derive from. Preliminary data on ultrastructure and gene expression suggest that the beta cells de-differentiated prior to cycling. Interestingly, the hypoxic microenvironment
also stimulated delta cells to de-differentiate, cycle and express insulin.
We hypothesize that the pancreas microenvironment following transient islet hypoxia alters the beta- and delta cell phenotype and, upon resolution becomes a rich source of signals that stimulate beta cell expansion.
This hypothesis will be evaluated by assessing (i) the (de-)differentiated phenotype of islet cells and
(ii) the metabolic switch in cycling islet cells that increase the beta cell mass.
Our data should pave the way towards development of an in vitro model for activation of the human beta cell cycle to increase the beta cell number, an obvious priority in diabetes research.
Effective start/end date1/01/1931/12/22

    Research areas

  • Cell Growth And Differentiation

    Flemish discipline codes

  • Cell division

ID: 44133394