Environmental diabetogens: biochemical links between microplastic exposure, endocrine disruption, and glucose metabolic dysfunction.

Abstract

The increase in the incidence of type 2 diabetes mellitus (T2DM) worldwide cannot be attributed solely to genetic and lifestyle factors, underscoring the growing role of environmental metabolic disruptors. Microplastics are increasingly being identified as potential environmental diabetogens, owing to the high risk of human exposure and the potential of microplastics to act as EDC carriers. This review aims to integrate the biochemical and molecular evidence for the association between microplastic exposure and the development of impaired glucose metabolism via endocrine, inflammatory, and metabolic signaling pathways. These microplastics and additives, such as bisphenols, phthalates, and POPs, interact with nuclear hormone receptors, including the estrogen receptor, peroxisome proliferator-activated receptor, and aryl hydrocarbon receptor, resulting in aberrant transcriptional control of genes involved in the regulation of metabolism. Microplastics exposure may cause oxidative stress-mediated activation of stress kinases, inhibition of insulin receptor substrate-1, suppression of PI3K-Akt signaling, GLUT4 translocation, and mitochondrial dysfunction, which together result in systemic insulin resistance. In addition, β-cell damage, systemic inflammation, and changes in the gut microbiome interfere with the regulation of glucose metabolism in the liver, muscle, and adipose tissues.