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Effects of Inorganic Arsenic on Type 2 Diabetes Mellitus In Vivo: the Roles and Mechanisms of miRNAs

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Abstract

Accumulating studies have shown that chronic exposure to iAs correlates with an increased incidence of diabetes. In recent years, miRNA dysfunction has emerged both as a response to iAs exposure and independently as candidate drivers of metabolic phenotypes such as T2DM. However, few miRNAs have been profiled during the progression of diabetes after iAs exposure in vivo. In the present study, high iAs (10 mg/L NaAsO2) exposure mice models of C57BKS/Leprdb (db/db) and C57BLKS/J (WT) were established through the drinking water, the exposure duration was 14 weeks. The results showed that high iAs exposure induced no significant changes in FBG levels in either db/db or WT mice. FBI levels, C-peptide content, and HOMA-IR levels were significantly increased, and glycogen levels in the livers were significantly lower in arsenic-exposed db/db mice. HOMA-β% was decreased significantly in WT mice exposed to high iAs. In addition, more different metabolites were found in the arsenic-exposed group than the control group in db/db mice, mainly involved in the lipid metabolism pathway. Highly expressed glucose, insulin, and lipid metabolism-related miRNAs were selected, including miR-29a-3p, miR-143-3p, miR-181a-3p, miR-122-3p, miR-22-3p, and miR-16-3p. And a series of target genes were chosen for analysis, such as ptp1b, irs1, irs2, sirt1, g6pase, pepck and glut4. The results showed that, the axles of miR-181a-3p-irs2, miR-181a-3p-sirt1, miR-22-3p-sirt1, and miR-122-3p-ptp1b in db/db mice, and miR-22-3p-sirt1, miR-16-3p-glut4 in WT mice could be considered promising targets to explore the mechanisms and therapeutic aspects of T2DM after exposure to high iAs.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

iAs:

Inorganic arsenic

FBG:

Fasting blood glucose

FBI:

Fasting blood insulin

IR:

Insulin resistance

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Funding

This study was funded by The National Natural Science Foundation of China (Grant no. 81872562).

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Authors and Affiliations

  1. Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China

    Jackson Sira, Xiaodan Zhang, Lin Gao, Jinyu Li, Caselia Akiti, Wei Zhang & Dianjun Sun

  2. Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618504), Harbin, 150081, China

    Jackson Sira, Xiaodan Zhang, Lin Gao, Jinyu Li, Caselia Akiti, Wei Zhang & Dianjun Sun

  3. Heilongjiang Provincial Key Laboratory of Trace Elements and Human Health, Harbin, 150081, China

    Jackson Sira, Xiaodan Zhang, Lin Gao, Jinyu Li, Caselia Akiti, Wei Zhang & Dianjun Sun

  4. Department of Biomedical Sciences, Faculty of Sciences, University of Ngaoundéré, P.O Box 454, Ngaoundéré, Cameroon

    Jackson Sira & Therese Martin Cheteu Wabo

  5. Department of Nutrition and Food Hygiene, Harbin Medical University, Harbin, 150081, China

    Therese Martin Cheteu Wabo

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  1. Jackson Sira
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Correspondence to Wei Zhang or Dianjun Sun.

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All experimental procedures were approved by the Committee on Ethics of Animal Experiments of Harbin Medical University (hrbmuecdc20200323), and complied with the institutional Guide for the Care and Use of Laboratory Animals. And all authors confirmed that this study is reported in accordance with ARRIVE guidelines.

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Sira, J., Zhang, X., Gao, L. et al. Effects of Inorganic Arsenic on Type 2 Diabetes Mellitus In Vivo: the Roles and Mechanisms of miRNAs. Biol Trace Elem Res 202, 111–121 (2024). https://doi.org/10.1007/s12011-023-03669-1

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