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Silencing circANKRD36 inhibits streptozotocin-induced insulin resistance and inflammation in diabetic rats by targeting miR-145 via XBP1

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Abstract

Background

Diabetes mellitus (DM) is defined as a group of metabolic diseases characterized by hyperglycemia, which results from a deficiency in insulin secretion and/or insulin action. In diabetic patients, type 2 diabetes mellitus (T2DM) is in the majority. We explored the effects of circANKRD36 on streptozotocin (STZ)-induced insulin resistance and inflammation in diabetic rats with the aim of uncovering the underlying mechanism.

Methods

STZ was used to induce the in vivo T2DM rat model. After circANKRD36 interference, blood glucose, insulin and adiponectin were respectively detected. Hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA) and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) were conducted to examine inflammation and apoptosis in T2DM rats, and western blot was used for detecting apoptosis-related proteins. The binding relationships among circANKRD36, miR-145 and XBP1 were examined by luciferase reporter assay.

Results

Results showed that circANKRD36 was expressed at a high level in T2DM rats, while silencing circANKRD36 led to decreased blood glucose and insulin, accompanied by increased adiponectin level, and ameliorating insulin resistance. Silencing circANKRD36 alleviated the inflammation and suppressed cell apoptosis in the pancreatic tissues of T2DM rats, which was abated by miR-145 inhibitor. The binding of miR-145 to XBP1 was then confirmed. Additionally, miR-145 inhibitor increased the level of XBP1 in T2DM rats, which was decreased in the presence of circANKRD36 silencing.

Conclusion

This study is the first to prove that silencing circANKRD36 inhibits STZ-induced insulin resistance and inflammation in diabetic rats by targeting miR- 145 via XBP1. The results warrant the importance of circRNAs as drug target and thereby pave way for the development of newer therapeutic measures for T2DM.

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All data generated or analyzed during this study are included in this published article.

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Funding

This work was supported by the Provincial Medical and Health Science and Technology Plan (NO. 2019KY019) and Regional Science Program of National Natural Science Foundation of China (NO. 81560766).

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Authors and Affiliations

  1. Department of Endocrinology, The Affiliated People’s Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China

    Jinger Lu

  2. Department of Chemoradiotherapy Centre, The Affiliated People’s Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China

    Linrong Pang

  3. Department of Infectious Disease, The Affiliated People’s Hospital of Ningbo University, Ningbo, 315040, Zhejiang, China

    Bo Zhang

  4. College of Physical Education, Jiangxi Normal University, Nanchang, 330022, Jiangxi, China

    Zhigang Gong

  5. College of Life Sciences, Jiangxi Normal University, No. 99 Ziyang Avenue, Nanchang, 330022, Jiangxi, China

    Chunhui Song

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Correspondence to Chunhui Song.

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Lu, J., Pang, L., Zhang, B. et al. Silencing circANKRD36 inhibits streptozotocin-induced insulin resistance and inflammation in diabetic rats by targeting miR-145 via XBP1. Inflamm. Res. 70, 695–704 (2021). https://doi.org/10.1007/s00011-021-01467-w

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  • DOI: https://doi.org/10.1007/s00011-021-01467-w

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