Amino Acids

, Volume 49, Issue 8, pp 1401–1414 | Cite as

Dityrosine administration induces dysfunction of insulin secretion accompanied by diminished thyroid hormones T3 function in pancreas of mice

  • Yin-Yi Ding
  • Zhu-Qing Li
  • Xiang-Rong Cheng
  • Yu-Mei Ran
  • Sha-Ji Wu
  • Yonghui Shi
  • Guowei Le
Original Article


Oxidized tyrosine products are commonly found in food with high protein content and have been demonstrated to cause damage of liver and kidney in our previous studies. Dityrosine (Dityr) is a typical oxidized tyrosine product. Due to its structural homology with thyroid hormones T3, we assumed that one of the endocrine systems most likely considered in connection with its disruption by Dityr may be the T3 action. T3 plays important roles in insulin synthesis, and thyroid hormone resistance (RTH) is associated with the impairment of glucose metabolism. Therefore, this study determined whether Dityr exposure impaired T3 function in pancreas leading to glucose metabolism disruption. After 10-week gavage with Dityr, mice exhibited impaired glucose tolerance and disturbed energy metabolism. The elevated free THs content in plasma, the up-regulation of THs synthesis-specific genes expressions in thyroid glands, and the increased thyroid follicles histology shapes and areas indicated that Dityr enhanced the THs synthesis in thyroid glands. In addition, Dityr-induced RTH, which reflected as elevated plasma free THs in the presence of unsuppressed thyroid stimulating hormone. The mRNA downregulation of membrane transporter of T3 (MCT8) and co-activator factors (RXRα, Src-1), together with the decreased protein level of thyroid hormone receptor β1 (TRβ1) in pancreas illustrated that the activation ability of T3 to downstream gene involved in insulin synthesis was suppressed by Dityr. In MIN-6 cell experiment, T3 improved glucose-stimulated insulin secretion by upregulating mRNA levels of insulin synthesis-related genes (Ins2, MafA, Pdx1) and T3 action-related genes, as well as increasing protein level of TRβ1. These data suggest that Dityr suppress T3-regulated insulin synthesis stimulated by glucose via an indirect way of decreasing sensibility to T3 in pancreas. All these findings indicate that Dityr can disrupt THs function in pancreas leading to glucose metabolism disorder.


Dityrosine C57BL/6J mice MIN-6 cells Glucose metabolism Energy metabolism Thyroid hormone resistance 



The author would like to thank Dr. Harimana Yves and Dr. Md Ramim Tanver Rahman from Jiangnan University for language polishing and Dr. Lingjie Sun from Jiangnan University for technical support in the measurement of whole body energy metabolism. This work is supported by the Chinese Nature Science Foundation (31571841), Natural Science Foundation of Jiangsu Providence, China (BK20140147).

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

And all animal treatments have been performed in accordance with the ethical standards laid down in the guidelines of National Institutes of Health Guide for the Care and Use of Laboratory Animals (China) and in the 1964 Declaration of Helsinki and its later amendments. All animal studies were approved by Laboratory Animals Ethics Committee of Jiangnan University.


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Copyright information

© Springer-Verlag Wien 2017

Authors and Affiliations

  1. 1.Food Nutrition and Functional Factors Research Center, School of Food Science and TechnologyJiangnan UniversityWuxiChina
  2. 2.The State Key Laboratory of Food Science and Technology, School of Food Science and TechnologyJiangnan UniversityWuxiChina

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