Arsenic exposure induces glucose intolerance and alters global energy metabolism
Year: 2017
Type: article
Abstract: Environmental pollutants acting as endocrine-disrupting chemicals (EDCs) are recognized as potential contributors to metabolic disease pathogenesis. One such pollutant, arsenic, contaminates the drinking water of ~100 million people globally and has been associated with insulin resistance and diabetes in epidemiological studies. Despite these observations, the precise metabolic derangements induced by arsenic remain incompletely characterized. In the present study, the impact of arsenic on in vivo metabolic physiology was examined in 8-wk-old male C57BL/6J mice exposed to 50 mg/l inorganic arsenite in their drinking water for 8 wk. Glucose metabolism was assessed via in vivo metabolic testing, and feeding behavior was analyzed using indirect calorimetry in metabolic cages. Pancreatic islet composition was assessed via immunofluorescence microscopy. Arsenic-exposed mice exhibited impaired glucose tolerance compared with controls; however, no difference in peripheral insulin resistance was noted between groups. Instead, early insulin release during glucose challenge was attenuated relative to the rise in glycemia. Despite decreased insulin secretion, pancreatic β-cell mass was not altered, suggesting that arsenic primarily disrupts β-cell function. Finally, metabolic cage analyses revealed that arsenic exposure induced novel alterations in the diurnal rhythm of food intake and energy metabolism. Taken together, these data suggest that arsenic exposure impairs glucose tolerance through functional impairments in insulin secretion from β-cells rather than by augmenting peripheral insulin resistance. Further elucidation of the mechanisms underlying arsenic-induced behavioral and β-cell-specific metabolic disruptions will inform future intervention strategies to address this ubiquitous environmental contaminant and novel diabetes risk factor.
Language: English
Subfield: Environmental Chemistry
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Funders: American Diabetes Association Research Foundation, University of Chicago, National Institutes of Health, Japan Society for the Promotion of Science, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G2405247988, Metabolic Impact of Fetal or Adult Exposure to Environmental Endocrine Disruptors, Selenoproteins in Arsenic-Induced Metabolic Dysfunction, ヒ素による糖代謝異常における膵α細胞の役割に関する研究, Diabetes Research and Training Center, University of Chicago Initiative for Maximizing Student Development (IMSD) - Renewal 01, ChicAgo Center for Health and EnvironmenT (CACHET), Diabetes Research and Training Center , Ruth L. Kirschstein National Research Service Award (NRSA) Institutional Research Training Grant (Parent T32)
OpenAlex ID: W2767897854