Metabolism And Adverse Effects of Arsenic In Genetically Diverse Mouse Strains

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  • May 15, 2019
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  • Ji, Jinglin
    • Affiliation: Gillings School of Global Public Health
Abstract
  • Through drinking water and food, millions of people worldwide are exposed to arsenic (As), which is a naturally occurring diabetogenic metalloid 13. Inorganic arsenic (iAs) exposure may disrupt glucose homeostasis leading to type 2 diabetes (T2D), including: (i) insulin resistance due to inhibition of insulin signaling, (ii) inhibition of insulin secretion, and (iii) aberrant micro RNA expression and activity 1, 2, 13. Arsenic methyltransferase (AS3MT) is the key enzyme in iAs detoxification pathway that determines disease outcome 3. Polymorphisms in AS3MT is the single most important genetic factor affecting iAs metabolism and susceptibility to adverse effects of iAs exposure, including diabetes. This study aims to examine the relationship between As3mt polymorphism and the adverse outcomes of iAs exposure in two Collaborative Cross (CC) mouse strains, CC021/Unc (CC021) and CC027/TauUnc (CC027), with different genetic backgrounds. Metabolic phenotype and susceptibility to adverse effects of iAs exposure are hypothesized to differ in CC021 and CC027 due to the differences in their hepatic As3mt expression and iAs metabolism (in liver). The metabolic/diabetic phenotype and iAs metabolism were assessed in both strains after 12 weeks of exposure to 100 ppb or 50 ppm iAs (sodium arsenite) in drinking water. The differences we observed between phenotypes of CC021 and CC027 mice were determined mainly by the genetic backgrounds of these strains and only to smaller extent by iAs exposure. Differences due to iAs exposure were found in weight gain, glycemia and insulin response to i.p. glucose injection, as well as in total As level in urine and in the percentage of total As represented by iAs. In future studies, we aim to identify other genes that underlie the susceptibility to iAs-associated T2D and establish a better mouse model in which As3mt expression and iAs metabolism resemble those in humans.
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  • Funding: Sarah Steele Danhoff Undergraduate Research Fund
  • Funding: William W. and Ida W. Taylor Honors Mentored Research Fellowship, Summer Undergraduate Research Fellowship
Advisor
  • Styblo, Mirek
Degree
  • Bachelor of Science in Public Health
Academic concentration
  • Nutrition
Honors level
  • Honors
Degree granting institution
  • University of North Carolina at Chapel Hill
Graduation year
  • 2019
Language
  • English

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