title: Par-4/NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity.
abstract: Apoptosis of islet β cells is a primary pathogenic feature of type 2 diabetes, and ER stress and mitochondrial dysfunction play important roles in this process. Previous research has shown that prostate apoptosis response-4 (Par-4)/NF-κB induces cancer cell apoptosis through endoplasmic reticulum (ER) stress and mitochondrial dysfunction. However, the mechanism by which Par-4/NF-κB induces islet β cell apoptosis remains unknown. We used a high glucose/palmitate intervention to mimic type 2 diabetes in vitro. We demonstrated that the high glucose/palmitate intervention induced the expression and secretion of Par-4. It also causes increased expression and activation of NF-κB, which induced NIT-1 cell apoptosis and dysfunction. Overexpression of Par-4 potentiates these effects, whereas downregulation of Par-4 attenuates them. Inhibition of NF-κB inhibited the Par-4-induced apoptosis. Furthermore, these effects occurred through the ER stress cell membrane and mitochondrial pathway of apoptosis. Our findings reveal a novel role for Par-4/NF-κB in islet β cell apoptosis and type 2 diabetes.
authors.affiliation: Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Wu
authors.initials: W
authors.lastname: QiNan
authors.affiliation: Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Gan
authors.initials: G
authors.lastname: XiaGuang
authors.affiliation: Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Lei
authors.initials: L
authors.lastname: XiaoTian
authors.affiliation: Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Deng
authors.initials: D
authors.lastname: WuQuan
authors.affiliation: Outpatient Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Ling
authors.affiliation: Endocrine Department, The First Affiliated Hospital of the Third Military Medical University, Chong Qing 400038, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Bing
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D016328:NF-kappa B; D010168:Palmitates; C101296:prostate apoptosis response-4 protein; D005947:Glucose