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Integrated analysis of gene modulation profile identifies pathogenic factors and pathways in the liver of diabetic mice

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Abstract

Purpose

Type-2 diabetes mellitus (T2D) is a metabolic disorder that can progress to a serious chronic disease and frequently develops in obese individuals in association with various pathogenic complications that shorten the lifespan of these patients. The liver is an important organ regulating lipid metabolism, which is damaged in both obesity and T2D; however, the specific pathways involved in these pathogenic effects remain unclear. Establishing a suitable animal model that effectively mimics the human biological condition is a critical factor to allow for precise identification of T2D-related genes.

Methods

The KK.Cg-Ay mouse strain is one such model that has offered insight into obesity-related T2D pathogenesis. To comprehensively assess the association between obesity and T2D, in the present study, we performed microarray analysis on liver tissue samples of KK.Cg-Ay and KK-α/α wild-type mice to examine differences in gene expression and methylation patterns and their related biological processes and pathways.

Results

We found that inflammation accompanied by abnormal lipid metabolism led to the spontaneous mechanism of obesity-induced diabetes, resulting in differential expression of some genes related to the terms of insulin resistance and glucose tolerance. Surprisingly, disruption of steroid biosynthesis strongly facilitated the diabetic pathogenesis. To support these findings, we highlighted some candidate genes and determined their relationships in biological networks of obesity-induced T2D.

Conclusion

These findings provide valuable reference data that can facilitate further detailed investigations to elucidate the pathogenic mechanism of obesity-induced diabetes in mice, which can be associated with the human condition to inform new prevention and treatment strategies.

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Acknowledgments

We are grateful to staffs within the research and clinical teams at Genetic Center, China Medical University Hospital for help in obtaining and processing samples for this research.

Funding

This work was supported by grants from China Medical University Hospital in Taiwan (DMR-107-048 and DMR-108-121.

Author information

Authors and Affiliations

  1. Graduate Institute of Biomedical Science, China Medical University, Taichung, 404, Taiwan

    Thai Quoc Tran

  2. Department of Biological Science and Technology, China Medical University, Taichung, 404, Taiwan

    Yuan-Man Hsu

  3. Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, 404, Taiwan

    Yu-Chuen Huang, Chao-Jung Chen, Wei-De Lin, Ying-Ju Lin, Wen-Ling Liao, Wei-Yong Lin, Jai-Sing Yang, Shih-Yin Chen & Fuu-Jen Tsai

  4. School of Chinese Medicine, China Medical University, Taichung, 404, Taiwan

    Yu-Chuen Huang, Chao-Jung Chen, Wei-De Lin, Ying-Ju Lin, Wen-Ling Liao, Wei-Yong Lin, Shih-Yin Chen & Fuu-Jen Tsai

  5. Institute of Biomedical Science, National Sun Yat-sen University, Kaohsiung, 80424, Taiwan

    Jinn-Chyuan Sheu

  6. Department of Medical Genetics, China Medical University Hospital, Taichung, 404, Taiwan

    Fuu-Jen Tsai

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  1. Thai Quoc Tran
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Tran, T.Q., Hsu, YM., Huang, YC. et al. Integrated analysis of gene modulation profile identifies pathogenic factors and pathways in the liver of diabetic mice. J Diabetes Metab Disord 18, 471–485 (2019). https://doi.org/10.1007/s40200-019-00453-8

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