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Updated: May 12, 2026
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals
Published on: June 25, 2018
Potential role of miR-128-1 modulating antioxidant NRF2 pathway in linking acrylamide exposure with type 2 diabetes
Zhiying Huo1, Jiahao Song1, Lieyang Fan2
1Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China; Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Health Effects of Environmental Pollution, Ministry of Ecology and Environment, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
Abstract:
Role of miR-128-1, an emerging therapeutic target of type 2 diabetes (T2D) and a targeted posttranscriptional suppressor of the antioxidant master nuclear factor erythroid 2-related factor 2 (NRF2), in linking acrylamide (ACR), a worldwide-concerning and lifelong-exposed pollutant, with T2D is unclear and warrants urgent elucidation. Epidemiologically, 482 Chinese adults from Wuhan-Zhuhai cohort were incorporated to evaluate the relationships among urinary ACR exposure biomarkers (N-acetyl-S-[2-carbamoylethyl]-L-cysteine [AAMA], N-acetyl-S-[2-carbamoyl-2-hydroxyethyl]-L-cysteine [GAMA], AAMA+GAMA [ΣUAAM], and GAMA/AAMA), plasma miR-128-1, and prevalent T2D by generalized-linear-models and the mediation role of miR-128-1 in ACR-T2D relationships by mediation analyses. Toxicologically, INS-1 cells were treated with ACR and miR-128-1 mimic/inhibitor for 24 h to explore the mechanism of miR-128-1 modulating antioxidant NRF2 pathway in ACR-related oxidative damage of β-cell function characterized by glucose-stimulated insulin secretion (GSIS). We uncovered linear positive relationships of ACR exposure biomarkers with miR-128-1 (β-coefficients: 0.63-1.45; P < 0.05) and T2D (odds ratio: 1.42-4.60; P < 0.05) and miR-128-1 with T2D (odds ratio: 1.34; P < 0.05) with elevated miR-128-1 mediated 18.39-24.54% of the ACR-T2D relationships. INS-1 cells treated with ACR showed NRF2 pathway activation and dose-dependent reduction in GSIS while elevations in miR-128-1 and oxidative stress (reactive oxygen species and malondialdehyde) levels. Compared to INS-1 cells treated with ACR+negative control, those treated with ACR+miR-128-1 mimic/inhibitor exhibited reduced/elevated mRNA and protein levels of NRF2 and downstream antioxidant factors, increased/decreased oxidative stress levels, and reduced/elevated GSIS. Overall, miR-128-1 might play a potential mechanism role in linking ACR exposure and T2D risk, possibly involving targeted suppression of antioxidant NRF2 pathway and oxidative impairment of β-cell function.
