title: Nr2e1 Deficiency Augments Palmitate-Induced Oxidative Stress in Beta Cells.
abstract: Nuclear receptor subfamily 2 group E member 1 (Nr2e1) has been regarded as an essential regulator of the growth of neural stem cells. However, its function elsewhere is unknown. In the present study, we generated Nr2e1 knockdown MIN6 cells and studied whether Nr2e1 knockdown affected basal beta cell functions such as proliferation, cell death, and insulin secretion. We showed that knockdown of Nr2e1 in MIN6 cells resulted in increased sensitivity to lipotoxicity, decreased proliferation, a partial G0/G1 cell-cycle arrest, and higher rates of apoptosis. Moreover, Nr2e1 deficiency exaggerates palmitate-induced impairment in insulin secretion. At the molecular level, Nr2e1 deficiency augments palmitate-induced oxidative stress. Nr2e1 deficiency also resulted in decreases in antioxidant enzymes and expression level of Nrf2. Together, this study indicated a potential protective effect of Nr2e1 on beta cells, which may serve as a target for the development of novel therapies for diabetes.
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Haohua
authors.initials: H
authors.lastname: Deng
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Yancheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Xiaokan
authors.initials: X
authors.lastname: Xiong
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Ma
authors.affiliation: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000633:toxicity*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency*; D016192:Resting Phase, Cell Cycle / Q000187:drug effects* / Q000235:genetics
chemical_list: D000975:Antioxidants; C490258:Nr2e1 protein, mouse; D018160:Receptors, Cytoplasmic and Nuclear; D019308:Palmitic Acid