title: Acetylcholinesterase is associated with apoptosis in β cells and contributes to insulin-dependent diabetes mellitus pathogenesis.
abstract: Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic β-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary β cells, and apoptotic pancreatic β cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary β cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic β cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Graduate Student School of Chinese Academy of Sciences, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Luyang
authors.initials: L
authors.lastname: Yu
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.forename: Yanan
authors.initials: Y
authors.lastname: Hou
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
authors.forename: Qin
authors.initials: Q
authors.lastname: Huang
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.forename: Lihe
authors.initials: L
authors.lastname: Guo
authors.forename: Qi
authors.initials: Q
authors.lastname: Ouyang
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D003401:Creatine / Q000097:blood; D003921:Diabetes Mellitus, Experimental; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006868:Hydrolysis; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013311:Streptozocin / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013311:Streptozocin; D000110:Acetylcholinesterase; D003401:Creatine