Abstract
BackgroundVitamin 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.MethodsPre- 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.ResultsFour 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.ConclusionsVitamin 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.
Highlights
Vitamin C, ascorbic acid or ascorbate, is well known as an antioxidant required for normal metabolic function of the body and is associated with a wide spectrum of biological processes (Mandl, Szarka & Banhegyi, 2009)
Several studies have reported a beneficial effect of vitamin C supplementation in type 2 diabetes mellitus (T2DM); a chronic metabolic disease associated with chronic hyperglycemia and excess free fatty acids (FFAs) (Hawkins et al, 2003)
Overproduction of reactive oxygen species (ROS) during the course of T2DM can cause DNA and protein damage, lipid peroxidation, cellular and vascular dysfunction leading to diabetic complications that have been associated with high levels of oxidative stress, as indicated by the markers malondialdehyde (MDA) and F2-Isoprostanes (F2IsoPs), and low levels of vitamin C (Bhatia et al, 2003; Johansen et al, 2005; Kaviarasan et al, 2009)
Summary
Vitamin C, ascorbic acid or ascorbate, is well known as an antioxidant required for normal metabolic function of the body and is associated with a wide spectrum of biological processes (Mandl, Szarka & Banhegyi, 2009). Several studies have reported a beneficial effect of vitamin C supplementation in type 2 diabetes mellitus (T2DM); a chronic metabolic disease associated with chronic hyperglycemia and excess free fatty acids (FFAs) (Hawkins et al, 2003). This complex disorder is characterized by insulin resistance in which the pancreas produces insufficient insulin or there is an ineffective response (American Diabetes, 2018). The validation study showed only miR-451a expression was significantly different from baseline with vitamin C supplementation. Bioinformatics analysis of the putative target genes of miR-451a indicated gene functions related to signaling pathways involved
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