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Tributyltin in male mice disrupts glucose homeostasis as well as recovery after exposure: mechanism analysis

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Abstract

Organotin compounds such as tributyltin (TBT) and triphenyltin can induce diabetes and insulin resistance. However, the development of diabetes caused by organotins and its underlying mechanisms remain unclear. In the present study, male KM mice were orally administered with TBT (0.5, 5, and 50 μg/kg) once every 3 days for 45 days. Their body weights increased and reached a significant difference compared to the control, and the fasting blood glucose levels were significantly elevated. The fasting levels of serum insulin and adiponectin increased, while glucagon levels decreased in the animals treated with TBT. The expression of the insulin receptor (IR) signaling cascade, including IR, IR substrate, phosphatidylinositol 3-kinase, Akt, and glucose transporter 4, was inhibited both in the skeletal muscle and the liver, which might be a main reason for the hyperglycemia and hyperinsulinemia. After removing the TBT stress for 60 days, the animals which had received exposure to TBT could recover normoglycemia, accompanied with a recovery of the suppressed IR signal pathway and fasting insulin levels. However, the fasting levels of serum adiponectin and glucagon were lower than that of the control mice, which would remain a potential risk inducing the disruption of glucose homeostasis.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21577113). Professor John Hodgkiss is thanked for his assistance with English.

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Authors and Affiliations

  1. State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, People’s Republic of China

    Bingshui Li, Jiaojiao Guo, Zhihui Xi, Jing Xu, Zhenghong Zuo & Chonggang Wang

  2. State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen, People’s Republic of China

    Chonggang Wang

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  1. Bingshui Li
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  2. Jiaojiao Guo
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  3. Zhihui Xi
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Li, B., Guo, J., Xi, Z. et al. Tributyltin in male mice disrupts glucose homeostasis as well as recovery after exposure: mechanism analysis. Arch Toxicol 91, 3261–3269 (2017). https://doi.org/10.1007/s00204-017-1961-6

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