title: FADD phosphorylation impaired islet morphology and function.
abstract: Previous studies have indicated that Fas-FasL pathway and its downstream caspase-8 can regulate islet mass and insulin secretion. As a classical adaptor in Fas-FasL signaling, Fas-associated death domain-containing protein (FADD) takes part in many non-apoptosis processes regulated by its phosphorylation. However, its role in islets has not been evaluated to date. Here, through comparative proteomics and bioinformatic analysis on FADD phosphorylated (FADD-D) and wild-type (WT) MEFs, we found three proteins involved in islet differentiation and function were dysregulated due to FADD phosphorylation. The mouse model of FADD-D, which mimics constitutive phosphorylated FADD expression in mice, was further analyzed to address this issue. We confirmed the proteomic results by immunohistological analyses on pancreatic islets. In addition, we found that FADD-D mice displayed decreased islet area, and the glucose stimulated insulin secretion (GSIS) of FADD-D islets was impaired. These data suggest a novel role of FADD in islet development and insulin secretion.
authors: The State Key Laboratory of Pharmaceutical Biotechnology, School of Stomatology and Affiliated Stomatological Hospital, Nanjing University, Nanjing, 210093, P. R. China.
authors: Chun
authors: C
authors: Yao
authors: Hongqin
authors: H
authors: Zhuang
authors: Wei
authors: W
authors: Cheng
authors: Yan
authors: Y
authors: Lin
authors: Pan
authors: P
authors: Du
authors: Bingya
authors: B
authors: Yang
authors: Xiaofeng
authors: X
authors: Huang
authors: Sheng
authors: S
authors: Chen
authors: Qingang
authors: Q
authors: Hu
authors: Zi-Chun
authors: ZC
authors: Hua
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053200:Fas-Associated Death Domain Protein / Q000235:genetics / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010766:Phosphorylation
chemical_list: C505534:Fadd protein, mouse; D053200:Fas-Associated Death Domain Protein; D007328:Insulin; D005947:Glucose