In:
Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-01-08)
Kurzfassung:
We have reported that autophagy is crucial for clearance of amyloidogenic human IAPP (hIAPP) oligomer, suggesting that an autophagy enhancer could be a therapeutic modality against human diabetes with amyloid accumulation. Here, we show that a recently identified autophagy enhancer (MSL-7) reduces hIAPP oligomer accumulation in human induced pluripotent stem cell-derived β-cells (hiPSC-β-cells) and diminishes oligomer-mediated apoptosis of β-cells. Protective effects of MSL-7 against hIAPP oligomer accumulation and hIAPP oligomer-mediated β-cell death are significantly reduced in cells with knockout of MiTF/TFE family members such as Tfeb or Tfe3 . MSL-7 improves glucose tolerance and β-cell function of hIAPP + mice on high-fat diet, accompanied by reduced hIAPP oligomer/amyloid accumulation and β-cell apoptosis. Protective effects of MSL-7 against hIAPP oligomer-mediated β-cell death and the development of diabetes are also significantly reduced by β-cell-specific knockout of Tfeb . These results suggest that an autophagy enhancer could have therapeutic potential against human diabetes characterized by islet amyloid accumulation.
Materialart:
Online-Ressource
ISSN:
2041-1723
DOI:
10.1038/s41467-020-20454-z
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2021
ZDB Id:
2553671-0
