title: First Identification of the Toxicity of Microcystins on Pancreatic Islet Function in Humans and the Involved Potential Biomarkers.
abstract: Microcystins (MCs) produced by cyanobacteria have been recognized as a major public health threat. However, the toxicity of MCs to humans is still largely unknown. In this study, we examined the changes in pancreatic islet function in fishers exposed to ambient levels of MCs at Lake Taihu and, using a mouse model, explored the molecular mechanisms involved in toxicity. MCs content in the serum of fishers tested positive, with a range from 0.10 to 0.64 μg/L. Both lower blood insulin levels (2.26 ± 0.96 μIU/mL) and impaired fasting glucose were found in participants from the Meiliang Bay area in Lake Taihu, where MC-LR levels were substantially greater than the MC threshold established by WHO for drinking water. Animal experiments showed that glucose level increased by 27.9% in mice exposed to 5 μg/kg bw and decreased by 41.5% in mice exposed to 20 μg/kg bw. Blood insulin levels declined by 21.9% and 56.2% in mice exposed to 5 and 20 μg/kg bw MC-LR, respectively, which was consistent with the results observed in fishers. Furthermore, the diabetes gene pdx1 and several other proteins (such as Ppp3ca, Ide, Marcks, Pgk1, Suclg1, Ndufs4) involved in insulin secretion were identified for the first time in mice following MC-LR exposure; these biomarkers were considered responsible for MC-LR induced islet dysfunction. This study suggests that subchronic exposure to environmental levels of MCs may increase the risk of the occurrence of diabetes in humans.
authors: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences , 73 East Beijing Road, Nanjing 210008, P. R. China.
authors: Yanyan
authors: Y
authors: Zhao
authors: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences , 73 East Beijing Road, Nanjing 210008, P. R. China.
authors: Qingju
authors: Q
authors: Xue
authors: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences , 73 East Beijing Road, Nanjing 210008, P. R. China.
authors: Xiaomei
authors: X
authors: Su
authors: State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences , 73 East Beijing Road, Nanjing 210008, P. R. China.
authors: Liqiang
authors: L
authors: Xie
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , 1037 Luoyu Road, Wuhan 430074, P. R. China.
authors: Yunjun
authors: Y
authors: Yan
authors: Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology , 1037 Luoyu Road, Wuhan 430074, P. R. China.
authors: Lixiao
authors: L
authors: Wang
authors: Annis Water Resources Institute, Grand Valley State University , 740 West Shoreline Drive, Muskegon, Michigan 49441, United States.
authors: Alan D
authors: AD
authors: Steinman
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D002681:China; D000458:Cyanobacteria / Q000378:metabolism; D060766:Drinking Water / Q000737:chemistry; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D060106:Lakes / Q000382:microbiology; D008297:Male; D008807:Mice, Inbred BALB C; D052998:Microcystins / Q000032:analysis* / Q000097:blood / Q000633:toxicity*; D036401:Toxicity Tests, Chronic / Q000379:methods; D014874:Water Pollutants, Chemical / Q000032:analysis
chemical_list: D015415:Biomarkers; D060766:Drinking Water; D052998:Microcystins; D014874:Water Pollutants, Chemical