AI Article Synopsis
- The study investigates how dedifferentiation of pancreatic β-cells might contribute to decreased β-cell mass in type 2 diabetes (T2D).
- Researchers used FGF2 growth factor to induce dedifferentiation in human β-cell lines and islets, observing a drop in β-cell markers and a rise in ectopic gene expression related to dedifferentiation.
- Findings suggest that enhanced FGF2 levels are present in the pancreas of T2D patients, linking FGF2 signaling to β-cell dedifferentiation and revealing potential new markers for this process.
Article 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, and stellate cells in pancreas from T2D patients, whereas FGFR1, SOX,9 and HES1 expression increased in islets from T2D patients.
Conclusions: We thus developed an FGF2-induced model of human β-cell dedifferentiation, identified new markers of dedifferentiation, and found evidence for increased pancreatic FGF2, FGFR1, and β-cell dedifferentiation in T2D.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985229 | PMC |
| http://dx.doi.org/10.1016/j.molmet.2018.02.002 | DOI Listing |
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