Modeling human pancreatic beta cell dedifferentiation.

ABSTRACT:

Objective

Dedifferentiation could explain reduced functional pancreatic β-cell mass in type 2 diabetes (T2D).

Methods

Here we model human β-cell dedifferentiation using growth factor stimulation in the human β-cell line, EndoC-βH1, and human pancreatic islets.

Results

Fibroblast growth factor 2 (FGF2) treatment reduced expression of β-cell markers, (INS, MAFB, SLC2A2, SLC30A8, and GCK) and activated ectopic expression of MYC, HES1, SOX9, and NEUROG3. FGF2-induced dedifferentiation was time- and dose-dependent and reversible upon wash-out. Furthermore, FGF2 treatment induced expression of TNFRSF11B, a decoy receptor for RANKL and protected β-cells against RANKL signaling. Finally, analyses of transcriptomic data revealed increased FGF2 expression in ductal, endothelial

SUBMITTER: Diedisheim M 

PROVIDER: S-EPMC5985229 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature