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Comparative analysis of the transcriptome of T2DM Bama mini-pigs with T2DM patients

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International Journal of Diabetes in Developing Countries Aims and scope Submit manuscript

Abstract

Objective

To compare the transcriptional differences between the T2DM-susceptible and T2DM-tolerant Bama mini-pigs and to determine the utility of Bama mini-pigs as an animal model for T2DM by comparing the transcriptomes of the animals with T2DM patients.

Methods

The skeletal muscle transcriptomes of healthy Guangxi Bama mini-pigs (CON), T2DM pigs (T2D), and non-T2DM pigs (NT2D) were determined by RNA sequencing.

Results

A total of 290 differentially expressed genes (DEGs) were detected in NT2D relative to the CON groups, 572 DEGs in T2D compared to CON, and 300 DEGs in T2D compared to NT2D. The RNA-seq data was verified by qPCR analysis of PGC1α, NR4A3, CSRP3, MYH7, MYH2, MYH1, GLUT4, PPARγ, LEP, ATP5H, UCP2, and MTOR transcripts. The DEGs in T2D Bama mini-pigs were mainly involved in signaling pathways associated with metabolism, cardiovascular diseases, infectious disease, cancer, inflammation and immune responses, cytoskeleton, and signal transduction. Comparative analysis of the transcriptomes of T2DM Bama mini-pigs and T2DM patients (GSE29221 dataset) revealed 17 differentially co-expressed genes that were assigned to 11 GO terms and 6 annotated pathways, including hypertrophic cardiomyopathy, dilated cardiomyopathy, thyroid cancer, cardiac muscle contraction, tight junction, and calcium signaling pathway, suggesting that the T2D Bama mini-pigs could be used on T2DM research in those pathways.

Conclusion

This study represents the first RNAseq transcriptome analysis in T2D Bama mini-pigs and provided a new perspective for the study on the human T2DM pathogenesis by using the T2DM model of Bama mini-pigs.

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Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res. 2007;125:451–72.

    CAS  PubMed  Google Scholar 

  2. Cefalu WT. Animal models of type 2 diabetes: clinical presentation and pathophysiological relevance to the human condition. ILAR J. 2006;47:186–98.

    Article  CAS  Google Scholar 

  3. Wagner JE, et al. Old world nonhuman primate models of type 2 diabetes mellitus. ILAR J. 2006;47:259–71.

    Article  CAS  Google Scholar 

  4. Engel H, et al. Rodent models of diet-induced type 2 diabetes mellitus: a literature review and selection guide. Diabetes Metab Syndr. 2019;13:195–200.

    Article  Google Scholar 

  5. Wang L, Wang C, Zhang R, et al. Phenotypic characterization of a novel type 2 diabetes animal model in a SHANXI MU colony of Chinese hamsters. Endocrine. 2019;65:61–72.

    Article  CAS  Google Scholar 

  6. Bellinger DA, Merricks EP, Nichols TC. Swine models of type 2 diabetes mellitus: insulin resistance, glucose tolerance, and cardiovascular complications. ILAR J. 2006;47:243–58.

    Article  CAS  Google Scholar 

  7. Vodicka P, et al. The miniature pig as an animal model in biomedical research. Ann N Y Acad Sci. 2005;1049:161–71.

    Article  Google Scholar 

  8. Yang L, et al. Genome-wide inactivation of porcine endogenous retroviruses (PERVs). Science. 2015;350:1101–4.

    Article  CAS  Google Scholar 

  9. Yan S, et al. A Huntingtin knockin pig model recapitulates features of selective neurodegeneration in Huntington’s disease. Cell. 2018;173:989–1002.

    Article  CAS  Google Scholar 

  10. Romagnuolo R, Masoudpour H, Porta-Sánchez A, et al. Human embryonic stem cell-derived cardiomyocytes regenerate the infarcted pig heart but induce ventricular tachyarrhythmias. Stem Cell Reports. 2019;12(5):967–81.

    Article  Google Scholar 

  11. Larsen MO, Rolin B. Use of the Gottingen minipig as a model of diabetes, with special focus on type 1 diabetes research. ILAR J. 2004;45:303–13.

    Article  CAS  Google Scholar 

  12. Johansen T, Hansen HS, Richelsen B, Malmlof R. The obese Gottingen minipig as a model of the metabolic syndrome: dietary effects on obesity, insulin sensitivity, and growth hormone profile. Comp Med. 2001;51:150–5.

    CAS  PubMed  Google Scholar 

  13. Wang A, Lan G, Guo Y. Genetic breeding of Guangxi Bama mini-pig. Lab Anim Sci. 2010;1:25.

    Google Scholar 

  14. Liu Y, et al. Severe insulin resistance and moderate glomerulosclerosis in a minipig model induced by high-fat/ high-sucrose/ high-cholesterol diet. Exp Anim. 2007;56:11–20.

    Article  CAS  Google Scholar 

  15. Niu M, et al. Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet. Asian-Australas J Anim Sci. 2017;30:1190–7.

    Article  CAS  Google Scholar 

  16. Wu Y, Zhang L, Liang J, et al. Comparative analysis on liver transcriptome profiles of different methods to establish type 2 diabetes mellitus models in Guangxi Bama mini-pig. Gene. 2018;673:194–200.

    Article  CAS  Google Scholar 

  17. Yan X, et al. iTRAQ and PRM-based quantitative proteomics in T2DM-susceptible and -tolerant models of Bama mini-pig. Gene. 2018;675:119–27.

    Article  CAS  Google Scholar 

  18. Jain P, et al. Systems biology approach reveals genome to phenome correlation in type 2 diabetes. PloS One. 2013;8:e53522.

    Article  CAS  Google Scholar 

  19. Sun SY, Liu ZP, Zeng T, Wang Y, Chen L. Spatio-temporal analysis of type 2 diabetes mellitus based on differential expression networks. Sci Rep. 2013;3:2268.

    Article  Google Scholar 

  20. Sales V, Patti ME. The ups and downs of insulin resistance and type 2 diabetes: lessons from genomic analyses in humans. Curr Cardiovasc Risk Rep. 2013;7:46–59.

    Article  Google Scholar 

  21. Stentz FB, Kitabchi AE. Transcriptome and proteome expressions involved in insulin resistance in muscle and activated T-lymphocytes of patients with type 2 diabetes. Genomics Proteomics Bioinformatics. 2007;5:216–35.

    Article  CAS  Google Scholar 

  22. Wu C, Xu G, Tsai SA, Freed WJ, Lee CT. Transcriptional profiles of type 2 diabetes in human skeletal muscle reveal insulin resistance, metabolic defects, apoptosis, and molecular signatures of immune activation in response to infections. Biochem Biophys Res Commun. 2017;482:282–8.

    Article  CAS  Google Scholar 

  23. Bugger H, Abel ED. Molecular mechanisms of diabetic cardiomyopathy. Diabetologia. 2014;57:660–71.

    Article  CAS  Google Scholar 

  24. Frati G, et al. An overview of the inflammatory signalling mechanisms in the myocardium underlying the development of diabetic cardiomyopathy. Cardiovasc Res. 2017;113:378–88.

    Article  CAS  Google Scholar 

  25. Chan KH, et al. Shared molecular pathways and gene networks for cardiovascular disease and type 2 diabetes mellitus in women across diverse ethnicities. Circ Cardiovasc Genet. 2014;7:911–9.

    Article  CAS  Google Scholar 

  26. Fu Y, Luo L, Luo N, Zhu X, Garvey WT. NR4A orphan nuclear receptors modulate insulin action and the glucose transport system: potential role in insulin resistance. J Biol Chem. 2007;282:31525–33.

    Article  CAS  Google Scholar 

  27. Walton, R.G. (University of Alabama at Birmingham, Graduate School, 2011).

  28. Zhu X, et al. Prostaglandin A2 enhances cellular insulin sensitivity via a mechanism that involves the orphan nuclear receptor NR4A3. Horm Metab Res. 2013;45:213–20.

    CAS  PubMed  Google Scholar 

  29. Weyrich P, et al. Common polymorphisms within the NR4A3 locus, encoding the orphan nuclear receptor Nor-1, are associated with enhanced beta-cell function in non-diabetic subjects. BMC Med Genet. 2009;10:77.

    Article  Google Scholar 

  30. Close AJ. Regulation of pancreatic β-cell life and death in the context of type 2 diabetes: study of the potential implication of the orphan nuclear receptor NR4A3/Nor1 and the NZF transcription factor ST18. 2017.

  31. Close AF, Dadheech N, Villela BS, Rouillard C, Buteau J. The orphan nuclear receptor Nor1/Nr4a3 is a negative regulator of beta-cell mass. J Biol Chem. 2019;294:4889–97.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the Scientific Research Project for the Colleges and universities of Guangxi (No.2020KY10033) and the Scientific Research Project for the high-level talents of Beibu Gulf University (No. 2019KYQD39).

Author information

Authors and Affiliations

  1. College of Animal Science and Technology, Guangxi University, Nanning, 530004, Guangxi, China

    Xueyu Yan, Jinglei Si, Yanjun Wu, Qinyang Jiang, Yafen Guo, Xiurong Yang, Jing Liang & Ganqiu Lan

  2. Guangxi Key Laboratory of Beibu Gulf Marine Biodiversity Conservation, College of Marine Sciences, Beibu Gulf University, Qinzhou, Guangxi, China

    Xueyu Yan

  3. Aquatic Product Technology Promotion Department of Qinzhou, Qinzhou, Guangxi, China

    Fangjie Zhong

  4. Institute of Laboratory Animal, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China

    Yanjun Wu

Authors
  1. Xueyu Yan
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  2. Jinglei Si
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  3. Fangjie Zhong
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  4. Yanjun Wu
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  5. Qinyang Jiang
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  6. Yafen Guo
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  7. Xiurong Yang
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  8. Jing Liang
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  9. Ganqiu Lan
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Contributions

Ganqiu Lan conceived the study and revised the manuscript. Xueyu Yan performed the experiments and wrote the manuscript. Jinglei Si assisted the experiments. Fangjie Zhong analyzed the data. Yanjun Wu assisted the experiments. Qinyang Jiang provided instructions and revised the manuscript. Yafen Guo provided instructions and advice. Xiurong Yang provided instructions and advice. Jing Liang provided instructions and advice.

Corresponding author

Correspondence to Ganqiu Lan.

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Ethics statement

All protocols were in accordance with the Guide for the Institutional Animal Care and Welfare Committee of the College of Animal Science and Technology, Guangxi University (Guangxi, China, permit no. GXU2013002).

Conflict of interest

The authors declare no competing interests.

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Yan, X., Si, J., Zhong, F. et al. Comparative analysis of the transcriptome of T2DM Bama mini-pigs with T2DM patients. Int J Diabetes Dev Ctries 42, 236–244 (2022). https://doi.org/10.1007/s13410-021-00981-1

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  • DOI: https://doi.org/10.1007/s13410-021-00981-1

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