The role of environmental pollutants in the global diabetes pandemic is an area of increasing scientific concern. This study investigates the disruptive effects of hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs), key metabolites of PAHs, on pivotal pathways of glucose metabolism. By combining multi-spectroscopic analyses, chemometric methods, and molecular dynamics simulations, the interactions of OH-PAHs with the intestinal enzyme α-glucosidase and their impact on non-enzymatic glycation of human serum albumin (HSA) were elucidated.
The results demonstrate that all tested OH-PAHs act as potent inhibitors of α-glucosidase, forming stable complexes with the enzyme and inducing conformational changes that suppress its catalytic activity. This inhibition may directly compromise carbohydrate digestion. Furthermore, under hyperglycemic conditions in vitro, OH-PAHs obviously accelerated the glycation of HSA. The mechanisms were identified as: competitive occupation of glycation sites, disruption of HSA's secondary structure, and enhancement of glyco-oxidation. These actions collectively led to increased formation of early, intermediate, and advanced glycation end products (AGEs).
It suggests that OH-PAHs may contribute to diabetes pathogenesis by targeting α-glucosidase and driving AGEs generation, thereby exacerbating glycemic control and its complications. This work provides new insights into understanding PAH-induced metabolic dysfunction and guides preventive strategies.
 

OH-PAHs,α-glucosidase,AGEs,Glucose metabolic disruption