A state-of-the-science review of arsenic’s effects on glucose homeostasis in experimental models

Felicia Castriota, Linda Rieswijk, Sarah Dahlberg, Michele A. La Merrill, Craig Steinmaus, Martyn T. Smith, Jen Chywan Wang

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

BACKGROUND: The prevalence of type 2 diabetes (T2D) has more than doubled since 1980. Poor nutrition, sedentary lifestyle, and obesity are among the primary risk factors. While an estimated 70% of cases are attributed to excess adiposity, there is an increased interest in understanding the contribution of environmental agents to diabetes causation and severity. Arsenic is one of these environmental chemicals, with multiple epidemiology studies supporting its association with T2D. Despite extensive research, the molecular mechanism by which arsenic exerts its diabetogenic effects remains unclear. OBJECTIVES: We conducted a literature search focused on arsenite exposure in vivo and in vitro, using relevant end points to elucidate potential mechanisms of oral arsenic exposure and diabetes development. METHODS: We explored experimental results for potential mechanisms and elucidated the distinct effects that occur at high vs. low exposure. We also performed network analyses relying on publicly available data, which supported our key findings. RESULTS: While several mechanisms may be involved, our findings support that arsenite has effects on whole-body glucose homeostasis, insulin-stimulated glucose uptake, glucose-stimulated insulin secretion, hepatic glucose metabolism, and both adipose and pancreatic b-cell dysfunction. DISCUSSION: This review applies state-of-the-science approaches to identify the current knowledge gaps in our understanding of arsenite on diabetes development.

Original languageEnglish (US)
Article number016001
JournalEnvironmental health perspectives
Volume128
Issue number1
DOIs
StatePublished - Jan 2020

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

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