Genetic and epigenetic mechanisms underlying arsenic-associated diabetes mellitus: a perspective of the current evidence

Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic beta-cell damage, pancreatic beta-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/ epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.