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Comparatively analyzing the liver-specific transcriptomic profiles in Kunming mice afflicted with streptozotocin- and natural food-induced type 2 diabetes mellitus

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Abstract

Background

Streptozotocin is a classic drug used to induce diabetes in animal models.

Objective

The aim of this study is to investigate the liver transcriptome of Kunming mice with diabetes induced by either streptozotocin (STZ) or Non-STZ.

Methods

Forty male mice were randomly assigned into four groups: Control (Ctr, standard diet), mHH (high fat and high carbohydrate diet), mHS (high fat and high carbohydrate diet for 4 weeks followed by 60 mg/kg STZ for 3 consecutive days) and mSH (60 mg/kg STZ for 3 consecutive days followed by a high fat and high carbohydrate diet for 12 weeks). All mice injected with STZ were identified as diabetic despite the sequential feeding of high fat and high carbohydrate diets.

Results

Only 7 of 13 mice in the mHH group met the diagnostic criteria for diabetes. The asting blood glucose (FBG) of the mHH, mHS, mSH and Ctrl groups was 13.27 ± 1.14, 15.01 ± 2.59, 15.95 ± 4.38 and 6.28 ± 0.33 mmol/L at the 12th week, respectively. Compared with the mHH group, transcription was elevated in 85 genes in the livers of mHS mice, while 21 genes were downregulated and 97 genes were upregulated in the mSH group while 35 genes were decreased. A total of 43 co-expressed genes were identified in the mHS vs mHH and mSH vs mHH groups. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses showed that two corporate GO terms and two KEGG pathways were significantly annotated in the STZ-treated groups. Both the GO term and pathway were related to the metabolism mediated by p53.

Conclusion

A high fat and high carbohydrate diet combined with a low dose of STZ can effectively induce diabetes in Kunming mice despite the abnormal expressions of genes in the liver. The differentially expressed genes were related to metabolism mediated by p53.

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Data availability

The underlying data supporting the results are available from the corresponding authors upon reasonable request.

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Funding

This work was supported by the Science and technology funds of the chairman of the Autonomous Region (No. 16449-10), the Science and Technology Major Special Project of Guangxi (No. Guike-AA17292002), the Guangdong Basic and Applied Basic Research Fund (2019A1515110280), the Foshan Science and Technology Innovation Project (1920001001203) and the Guangdong Science and Technology Innovation Strategy Fund (The Special Fund for “Climbing Plan”; pdjh2020a0616).

Author information

Author notes

  1. Yanjun Wu and Xiangxing Zhu have contributed equally to this work.

Authors and Affiliations

  1. Institute of Laboratory Animal Research, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China

    Yanjun Wu & Shuguang Wu

  2. College of Animal Science & Technology, Guangxi University, Nanning, 530004, China

    Yanjun Wu, Arome Solomon Odiba, Jing Liang & Ganqiu Lan

  3. School of Medicine, Foshan University, Foshan, 528225, China

    Xiangxing Zhu, Zisheng Lin, Jiancong Wen & Daoyuan Gong

Authors
  1. Yanjun Wu
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Contributions

GQL and YJW conceived and designed the experiments; YJW, XXZ and JL performed the experiments and analyzed the data; ASO, ZSL, JCW and DYG participated in experiment assistant. GQL, YJW, XXZ and SGW drafted the manuscript. All authors participated in discussions of the results and reviewed the manuscript.

Corresponding author

Correspondence to Ganqiu Lan.

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Conflict of interest

Author Yanjun Wu declares that he has no conflict of interest. Author Xiangxing Zhu declares that he has no conflict of interest. Author Arome Solomon Odiba declares that he has no conflict of interest. Author Zisheng Lin declares that he has no conflict of interest. Author Jiancong Wen declares that he has no conflict of interest. Author Daoyuan Gong declares that he has no conflict of interest. Author Jing Liang declares that he has no conflict of interest. Author Shuguang Wu declares that she has no conflict of interest. Author Ganqiu Lan declares that he has no conflict of interest.

Ethical approval

All of the animal procedures used in this study were carried out in accordance with the Guide for Care and Use of Laboratory Animals (8th edition, released by the National Research Council, USA), and were approved by the Animal Care & Welfare Committee of Guizhou University of Traditional Chinese Medicine and Foshan University (Approval No. 2019020). All of the surgical procedures were performed under anesthesia by a veterinarian, and all efforts were made to minimize animal suffering.

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Wu, Y., Zhu, X., Odiba, A.S. et al. Comparatively analyzing the liver-specific transcriptomic profiles in Kunming mice afflicted with streptozotocin- and natural food-induced type 2 diabetes mellitus. Mol Biol Rep 49, 1369–1377 (2022). https://doi.org/10.1007/s11033-021-06970-1

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