Inhibition and Recovery of Glucose-Stimulated Insulin Secretion in Pancreatic Beta Cells Chronically Exposed to Trivalent Arsenicals

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  • February 26, 2019
Creator
  • Ostrom, William
    • Affiliation: Gillings School of Global Public Health, Department of Nutrition
Abstract
  • Diabetes is a leading cause of global morbidity and mortality and the number of those affected by diabetes is growing at an alarming rate. Although Type 2 diabetes (T2D) is typically associated with obesity, environmental diabetogens like arsenite (iAsIII) and its trivalent methylated metabolites methylarsonite (MAsIII) and dimethylarsinite (DMAsIII) may be contributing to the global diabetes epidemic. Previous studies from our lab have shown that these trivalent arsenicals act directly on pancreatic beta-cells by reducing glucose-stimulated insulin secretion (GSIS) and thus contributing to the development of diabetes. Previous in vitro and epidemiological studies from our lab have shown that the diabetogenic effects of arsenic may be reversible following removal of exposure. In this study, we examined the effects of 24-hour exposure to iAsIII, MAsIII or DMAsIII on GSIS in a pancreatic beta-cell line, INS-1 832/13 and tested if the inhibitory effects of arsenic exposure on β-cell function are reversible. GSIS was significantly inhibited by exposure to 2 µM AsIII, ≥0.375 µM MAsIII and 2 µM DMAsIII. After a 24-hour recovery period in As-free media, complete recovery of GSIS was observed for cells previously exposed to doses of iAsIII and MAsIII which significantly inhibited GSIS. Preliminary data from this study also show that Ca2+ influx into pancreatic beta-cells was significantly decreased by 0.375 µM MAsIII exposure. The inhibition of Ca2+ influx was also reversed after a recovery period in As-free media. Data from this study confirm reversibility results reported by previous studies from our lab. In summary, results from this study show that pancreatic β-cells are a key target for the diabetogenic effects of trivalent arsenicals, and that these diabetogenic effects are reversible.
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  • In Copyright
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  • Funding: None
Advisor
  • Styblo, Miroslav
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
  • 2017
Language
  • English

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