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- W2894035911 abstract "Endoplasmic reticulum stress has been considered a major cause of pancreatic β-cell dysfunction and apoptosis leading to diabetes. Glucagon-like peptide-1 receptor activation and chemical chaperones have been known to reduce endoplasmic reticulum stress and improve β-cell function and survival. The purpose of this study was to prepare and evaluate the chemical chaperone tauroursodeoxycholic acid-conjugated exendin-4 as a protective agent for pancreatic β-cells. Mono-tauroursodeoxycholic acid-Lys27-exendin-4 conjugate (TUM1-Ex4) showed better receptor binding affinity than other conjugates with strong in vitro insulinotropic activity in rat pancreatic β-cells and in vivo hypoglycemic activity in type 2 diabetic db/db mice. In INS-1 cells under endoplasmic reticulum stress induced by thapsigargin, TUM1-Ex4 promoted cell survival in a dose-dependent manner. In western blot analysis, TUM1-Ex4 reduced the expression of the endoplasmic reticulum stress marker GRP78 and phosphorylation of the translation initiation factor eIF2α. These results reveal that TUM1-Ex4 accelerates translational recovery and contributes to β-cell protection and survival. The present study indicates that the chemical chaperone-coupled glucagon-like peptide-1 receptor agonist is a feasible therapeutic strategy to enhance β-cell function and survival." @default.
- W2894035911 created "2018-10-05" @default.
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- W2894035911 date "2018-12-01" @default.
- W2894035911 modified "2023-10-18" @default.
- W2894035911 title "Chemical chaperone-conjugated exendin-4 as a cytoprotective agent for pancreatic β-cells" @default.
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- W2894035911 doi "https://doi.org/10.1016/j.biocel.2018.09.018" @default.
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