The crucial role of thioredoxin interacting protein in the liver insulin resistance induced by di (2-ethylhexyl) phthalates.

Abstract

The widespread usage of plastic products in human life has led to extensive exposure to plasticizers and resulted in serious health problems for humans, which has become a focus of toxicology research in the world. We aimed to explore the potential mechanism of liver insulin resistance induced by di(2-ethylhexyl) phthalate (DEHP) and working on a novel treatment to alleviate insulin resistance caused by excessive exposure to DEHP. For this purpose, in vivo and in vitro experiments were conducted, and the pivotal factors in the insulin signaling pathway were analyzed. In vivo study showed DEHP could lead to liver injury and insulin resistance. DEHP could break the balance of oxidative stress and cause accumulation of inflammatory factors. Genomics and proteomics experiment results revealed that DEHP could inhibit the mRNA and protein expression of insulin receptor, insulin receptor substrate, PI3K/Akt/mTOR, and glucose transporter 4. Nevertheless, the liver insulin resistance induced by DEHP could be reversed by Verapamil (thioredoxin interacting protein (TXNIP) inhibitor). Thus, we confirmed that DEHP caused insulin resistance by affecting the TXNIP in liver, further damaging the conduction of insulin signaling pathway. Therefore, adding Verapamil to the treatment of patients with insulin resistance due to plasticizers might be more effective.

• Authors: Wang Zhang, Peng Xu, Jing-Ya Li
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 164 Pg. 113045 (Jun 2022) ISSN: 1873-6351 [Electronic] England
• PMID: 35460826 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier Ltd. All rights reserved.

Chemical References

• Insulin
• Phthalic Acids
• Plasticizers
• Thioredoxins
• phthalic acid
• Diethylhexyl Phthalate
• Verapamil

Topics

• Diethylhexyl Phthalate (metabolism)
• Humans
• Insulin (metabolism)
• Insulin Resistance
• Liver
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phthalic Acids
• Plasticizers (toxicity)
• Thioredoxins (genetics, metabolism)
• Verapamil (pharmacology)