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. 2023 Apr 12;131(4):047009. doi: 10.1289/EHP11896

Figure 7.

Figure 7A is an illustration depicting the molecular initiating events in response to exposure to the key organophosphate esters, including T M P P, T P H P, D B P, D P H P and the subsequent series of key events, for example, multiple signal transduction and metabolic pathway perturbations. The key events -1 are at the molecular or cellular level and result in impaired biological functions, and the key events -2 are at the organ or system level, including inflammation, insulin secretion, fatty acid oxidation, oxidative stress, apoptosis or autophagy, glycogen synthesis, glucose uptake, and energy metabolism, which ultimately induce glycometabolic disorder-related adverse outcomes. The genes and metabolites include up with significance, down with significance, up, and down Figure 7B is an illustration, depicting the putative biological mechanisms that mediate the linkages between organophosphate esters exposure and apical type 2 diabetes outcome. The illustration is divided into three parts, namely, Exposure, Pathway, and Outcome. Exposure includes T M P P, T P H P, D B P, and D P H P. The pathway depicts the reactions on P 13 K-A K T signaling, insulin receptor signaling, apoptosis, autophagy, and oxidative stress; P P R A lowercase alpha and R X R lowercase alpha activation; leptin signaling in obesity; glucocorticoids regulation; insulin secretion signaling, and G lowercase alpha 12 of 13 signaling. In the outcome, insulin resistance plus hyperglycemia leads to type 2 diabetes mellitus.

AOP linking OPE exposure and adverse outcome and schematic of the putative biological mechanisms of OPEs exposure–induced type 2 diabetes outcome. (A) An AOP diagram depicting the MIEs in response to exposure to the key OPEs and the subsequent series of KEs, for example, multiple signal transduction and metabolic pathway perturbations (KE-1 at the molecular/cellular level) and impaired biological functions (KE-2 at the organ/system level), which ultimately induced glycometabolic disorder-related adverse outcomes. Alterations of genes (blue) and metabolites (purple) are represented with colored boxes. (B) Schematic of the putative biological mechanisms that mediate the linkages between OPEs exposure and apical type 2 diabetes outcome. Note: AOP, adverse outcome pathway; KEs, key events; MIEs, molecular initiating events; OPE, organophosphate ester; T2DM, type 2 diabetes mellitus.