Vitamin C supplementation reduces expression of circulating miR-451a in subjects with poorly controlled type 2 diabetes mellitus and high oxidative stress

Laongthip Ruknarong; Chongchira Boonthongkaew; Nisa Chuangchot; Amonrat Jumnainsong; Naruemon Leelayuwat; Apinya Jusakul; Silvana Gaudieri; Chanvit Leelayuwat

doi:10.7717/peerj.10776

Vitamin C supplementation reduces expression of circulating miR-451a in subjects with poorly controlled type 2 diabetes mellitus and high oxidative stress

PeerJ. 2021 Feb 4:9:e10776. doi: 10.7717/peerj.10776. eCollection 2021.

Authors

Laongthip Ruknarong^{1

2

3}, Chongchira Boonthongkaew^{2

3}, Nisa Chuangchot^{1

2

3}, Amonrat Jumnainsong^{1

4}, Naruemon Leelayuwat^{3

5}, Apinya Jusakul^{1

4}, Silvana Gaudieri^{6

7

8}, Chanvit Leelayuwat^{1

4}

Affiliations

¹ Centre for Research and Development of Medical Diagnostic Laboratories (CMDL), Faculty of Associated Medical Sciences, Khon Kaen University, Khon kean, Thailand.
² Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.
³ Exercise and Sport Sciences Development and Research Group (ESRG), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
⁴ Department of Clinical Immunology and Transfusion Sciences, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen, Thailand.
⁵ Graduate School, Khon Kaen University, Khon Kaen, Thailand.
⁶ School of Human Sciences, University of Western Australia, Perth, Western Australia, Australia.
⁷ Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia.
⁸ Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN, United States of America.

Abstract

Background: Vitamin C is an essential element required for normal metabolic function. We investigated the effect of vitamin C supplementation on circulating miRNA (miR) expression in subjects with poorly controlled type 2 diabetes mellitus (T2DM). Changes in miR expression were also correlated with clinical measures of disease.

Methods: Pre- and post-vitamin C supplementation samples from five participants who had increased vitamin C levels, improved oxidative status and polymorphonuclear (PMN) function after receiving 1,000 mg of vitamin C daily for six weeks were screened for miRNA expression using the NanoString miRNA assay. Differences in miRNA expression identified from the miRNA screen were validated by qRT-PCR.

Results: Four miRNAs showed significantly different expression post-vitamin C supplementation relative to baseline, including the down-regulation of miR-451a (-1.72 fold change (FC), p = 0.036) and up-regulation of miR-1253 (0.62 FC, p = 0.027), miR-1290 (0.53 FC, p = 0.036) and miR-644a (0.5 FC, p = 0.042). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. MiR-451a expression was negatively correlated with vitamin C levels (r = - 0.497, p = 0.049) but positively correlated with levels of malondialdehyde (MDA) (r = 0.584, p = 0.017), cholesterol (r = 0.564, p = 0.022) and low-density lipoproteins (LDL) (r = 0.522, p = 0.037). Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved in cellular processes, such as the mammalian target of rapamycin (mTOR) signaling pathway.

Conclusions: Vitamin C supplementation altered circulating miR-451a expression. The results from this pilot study suggest that miRNAs could be used as biomarkers to indicate oxidative status in subjects with T2DM and with poor glycemic control and could lead to a novel molecular strategy to reduce oxidative stress in T2DM.

Keywords: Oxidative stress; Type 2 diabetes; Vitamin C; miRNA; miRNA array.

Grants and funding

This work was supported by The Royal Golden Jubilee (RGJ) Ph.D. Programme (PHD/0045/2557). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.