Fig. 1

The proposed pathway for AhR-mediated glucose hemostasis and DM by environmental pollutants. AhR is expressed in various tissues, including the pancreas, liver, and adipose tissues, making it a crucial receptor in many physiological and pathological processes involved in insulin secretion and glucose metabolism. Mechanistically, upon binding of TCDD to AhR, the activated receptor translocates to the nucleus after dissociation from its inhibitory protein HSP90 and XAP2. The activated receptor interacts with type 2 basic helix–loop–helix/PER-ARNT-SIM (bHLH-PAS) protein, AhR nuclear translocator (ARNT). The resulting complex selectively binds to a specific sequence on CYP1A1 DNA. known as the xenobiotic responsive element (XRE), leading to transcriptional induction of specific genes involved in xenobiotic metabolism, such as CYP1A1 and CYP1B1. Induction of AhR downstream targets CYP1A1 and CYP1B1 directly or indirectly induce impaired glucose hemostasis and insulin secretion. Created by bioRender.com