# Gender-Specific Effects of Arsenic in Diabetes

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $393,675

## Abstract

Project Summary/Abstract
Inorganic arsenic (iAs) is the top chemical on the ATSDR priority list of hazardous substances. Its role in
carcinogenesis has been studied extensively, whereas its role in metabolic disorders has not. Recent human
epidemiology studies have identified correlation between type 2 diabetes (T2D) and arsenic exposure. We
found that the effect of iAs on metabolism shows sexual dimorphism in mice, with male mice more susceptible
to glucose intolerance and female mice more susceptible to changes in hepatic lipid accumulation. We
hypothesize that the metabolic and transcriptomic effect of iAs is modulated by estrogen through estrogen
receptor (ER) and its co-repressor complex containing histone deacetylase 3 (HDAC3), which accounts for
gender-specific effects of iAs in diabetes. We will determine whether loss of estrogen receptor (ER) increases
susceptibility to iAs-induced diabetes; whether gain-of-function of ER through genetic manipulation of HDAC3
protects against iAs-induced diabetes; how ER modulates iAs-induced transcriptomic changes, and whether
such modulation can be mimicked by HDAC inhibitors (HDIs). Our study addresses the knowledge gap in
gender-specific susceptibility to diseases or environmental toxins, and has obvious translational value in
prevention and treatment against environmental hazards in both genders, given the availability of selective
estrogen receptor modulators (SERMs) and epigenome-modifying HDIs.

## Key facts

- **NIH application ID:** 9984848
- **Project number:** 5R01ES027544-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Zheng Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $393,675
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984848

## Citation

> US National Institutes of Health, RePORTER application 9984848, Gender-Specific Effects of Arsenic in Diabetes (5R01ES027544-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9984848. Licensed CC0.

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