Type 2 Diabetes Induced by Changes in Proteomic Profiling of Zebrafish Chronically Exposed to a Mixture of Organochlorine Pesticides at Low Concentrations

Yan Gao, Hyojin Lee, Sangkyu Lee and Ki-Tae Kim
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Yan Gao: BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea
Hyojin Lee: Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Korea
Sangkyu Lee: BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea
Ki-Tae Kim: Department of Environmental Engineering, Seoul National University of Science and Technology, Seoul 01811, Korea

IJERPH, 2022, vol. 19, issue 9, 1-14

Abstract: Effect of organochlorine pesticides (OCPs) mixtures on development of type 2 diabetes mellitus (T2DM) and the underlying mechanism, especially at protein levels, are largely unknown. We exposed a mixture of five OCPs to zebrafish at concentrations of 0, 0.05, 0.25, 2.5, and 25 μg/L for 12 weeks. Differentially expressed proteins (DEPs) were quantitatively identified in female zebrafish livers, and its functional study was conducted. The significantly high glucose and low insulin levels were observed only at 0.05 μg/L, linking to the different pattern of DEPs than other concentrations. A total of 1082 proteins was quantified, of which 321 proteins formed 6 clusters in protein dynamics analysis. The enriched pathways in cluster 3 showing distinct pattern of DEPs could explain the nonlinear response at 0.05 μg/L, indicating that OCP mixtures adversely affected proteins associated with mitochondrial function and energy metabolism. We proposed a feasible mechanism that decrease in expression of aldehyde dehydrogenase led to abnormal accumulation of aldehydes, reducing expression of glyceraldehyde 3-phosphate dehydrogenase, and resulting in disruption of glucose homeostasis. Our findings help to better understand the causality of T2DM by exposure to OCP mixtures and to identify biomarkers in the protein expression level.

Keywords: organochlorine pesticide mixtures; type 2 diabetes mellitus; zebrafish; proteomics; aldehyde dehydrogenase 2; glyceraldehyde 3-phosphate dehydrogenase (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2022
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