Metabolomic Profiles of Pancreatic β-Cells and Islets Exposed to Arsenic, part I β-Cells

ABSTRACT: Type-2 diabetes (T2D) is a complex metabolic disorder that affects hundreds of millions of people world-wide and is a growing public health concern. Despite recent advances in T2D research, the etiology of this disease and the mechanisms underlying the metabolic defects remain poorly understood. While obesity is thought to be the main cause for the rising prevalence of T2D, obesity alone cannot explain differences in the trends of T2D among different geographical regions and populations. Growing evidence suggests that environmental exposures to toxic and diabetogenic substances must play important roles. Inorganic arsenic (iAs) is a naturally occurring toxic metalloid. Hundreds of millions of people worldwide are exposed to unsafe levels of iAs in drinking water and food. iAs is a potent carcinogen, but iAs exposure has also been linked to increase risk of T2D. While the link between iAs exposure and T2D is well-established, the mechanisms underlying the diabetogenic effects of iAs exposure remain unclear. Results of our previously published and ongoing studies suggest that pancreatic β-cells are a primary target for iAs and its metabolites and that impaired insulin secretion by β-cells is the mechanism by which iAs exposure leads to diabetes. The proposed project will use metabolomics to identify metabolic pathways in β-cells that are targeted by iAs and its metabolites, monomethyl-As (MAs) and dimethyl-As (DMAs). The metabolomics data combined with results of our ongoing mechanistic studies will provide a comprehensive picture of the metabolic dysfunction leading to the development of diabetes in individuals exposed to iAs and of the molecular mechanisms that underlie this dysfunction. Identifying the affected pathways and mechanisms will ultimately help to improve strategies for prevention and/or treatment of T2D associated with chronic exposure to iAs.

ORGANISM(S): Mouse Mus Musculus

TISSUE(S): Cultured Cells

DISEASE(S): Diabetes

SUBMITTER: Susan Sumner  

PROVIDER: ST001266 | MetabolomicsWorkbench | Mon Apr 15 00:00:00 BST 2019

REPOSITORIES: MetabolomicsWorkbench