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

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.

Diabetes mellitus and serum organochlorine pesticides mixtures in Mexican women

“…Individually, it has been observed that some OCP have diabetogenic effects at high doses to which humans would not normally be exposed [ 41 ]. More recently, it has been shown that OCP mixtures at low doses have diabetogenic effects through one or several mechanisms such as: the production of reactive oxygen species, mitochondrial dysfunction, insulin resistance, inhibition of insulin secretion, and alterations in lipid metabolism [ 42 – 45 ]. However, more information is required on the possible interactions between the underlying biological mechanisms of DM due to concomitant exposure to low doses of OCP.…”

State of the Art of Genomic Technology in Toxicology: A Review

“…Glyceraldehyde 3-phosphate dehydrogenase expression is also decreased, which disturbs glucose homeostasis. These effects are caused by the proteome profiling of zebrafish livers using isobaric tags multiplexed quantitative proteomics [15].…”