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Title: Arsenic exposure induces glucose intolerance and alters global energy metabolism.

Authors: Kirkley, Andrew G; Carmean, Christopher M; Ruiz, Daniel; Ye, Honggang; Regnier, Shane M; Poudel, Ananta; Hara, Manami; Kamau, Wakanene; Johnson, Daniel N; Roberts, Austin A; Parsons, Patrick J; Seino, Susumu; Sargis, Robert M

Published In Am J Physiol Regul Integr Comp Physiol, (2018 Feb 01)

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.

PubMed ID: 29118024 Exiting the NIEHS site

MeSH Terms: Animals; Arsenites/toxicity*; Biomarkers/blood; Blood Glucose/drug effects*; Blood Glucose/metabolism; Endocrine Disruptors/toxicity*; Energy Metabolism/drug effects*; Glucose Intolerance/blood; Glucose Intolerance/chemically induced*; Glucose Intolerance/pathology; Insulin Resistance; Insulin-Secreting Cells/drug effects*; Insulin-Secreting Cells/metabolism; Insulin-Secreting Cells/pathology; Insulin/blood*; Male; Mice, Inbred C57BL; Secretory Pathway/drug effects; Sodium Compounds/toxicity*; Water Pollutants, Chemical/toxicity*

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