title: Arsenic induces diabetic effects through beta-cell dysfunction and increased gluconeogenesis in mice.
abstract: Arsenic as a potential risk factor for type 2 diabetes has been received attention recently. However, the roles of arsenic on development of diabetes are unclear. In this study, we compared the influences of inorganic arsenic (iAs) on normal and diabetic mice by systems toxicology approaches. Although iAs exposure did not change glucose tolerance in normal mice, it caused the pancreatic β-cell dysfunction and increased gluconeogenesis and oxidative damages in liver. However, iAs exposure worsened the glucose tolerance in diabetic mice, which might be due to increased gluconeogenesis and impairment of pancreatic β-cell function. It is interesting that iAs exposure could improve the insulin sensitivity based on the insulin tolerance testing by the activation of glucose uptake-related genes and enzymes in normal and diabetic individuals. Our data suggested that iAs exposure could cause pre-diabetic effects by altering the lipid metabolism, gluconeogenesis and insulin secretion in normal individual, and worsen diabetic effects in diabetes individual by these processes. Insulin resistance might be not the reason of diabetic effects caused by iAs, indicating that mechanism of the diabetogenic effects of iAs exposure is different from the mechanism associated with traditional risk factors (such as obesity)-reduced type 2 diabetes.
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Su
authors.initials: S
authors.lastname: Liu
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Guo
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Wu
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Yu
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Xuxiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State key laboratory of Pollution control and resource reuse, School of the Environment, Nanjing University, Nanjing, 210023, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
mesh_terms: D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D002149:Energy Intake / Q000187:drug effects; D005943:Gluconeogenesis / Q000187:drug effects*; D018149:Glucose Intolerance; D007249:Inflammation / Q000139:chemically induced; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D014874:Water Pollutants, Chemical; D001151:Arsenic