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Publication : Attenuation of unfolded protein response and apoptosis by mReg2 induced GRP78 in mouse insulinoma cells.

First Author  Liu L Year  2014
Journal  FEBS Lett Volume  588
Issue  11 Pages  2016-24
PubMed ID  24801175 Mgi Jnum  J:211052
Mgi Id  MGI:5573075 Doi  10.1016/j.febslet.2014.04.030
Citation  Liu L, et al. (2014) Attenuation of unfolded protein response and apoptosis by mReg2 induced GRP78 in mouse insulinoma cells. FEBS Lett 588(11):2016-24
abstractText  Murine regenerating (mReg) genes have been implicated in preserving islet cell biology. Expanding on our previous work showing that overexpression of mReg2 protects MIN6 insulinoma cells against streptozotocin-induced apoptosis, we now demonstrate that mReg2 induces glucose-regulated peptide 78 (GRP78) expression via the Akt-mTORC1 axis and protects MIN6 cells against ER stress induced by thapsigargin and glucolipotoxicity. Activation of mTORC1 activity results from both mReg2-induced increased mTOR phosphorylation as well as increased expression of Raptor and GbetaL. Inhibition of Akt and mTORC1 blunted the ability of mReg2 to induce GRP78 and attenuate unfolded protein response (UPR). Knockdown of GRP78 sensitized the cells overexpressing mReg2 to UPR without affecting its ability to activate Akt-mTORC1 signaling. Induced expression of mReg2 may protect insulin producing cells from ER stress in diabetes.
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