Dataset Information

Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with Prediabetes and Type 2 Diabetes Mellitus.

ABSTRACT: Hyperglycemia-mediated oxidative stress impedes cell-reparative process like autophagy, which has been implicated in impairment of ?-cell function in type 2 diabetes mellitus (T2DM). However, the role of mitophagy (selective mitochondrial autophagy) in progression of hyperglycemia remains elusive. This study aimed to assess the impact of increasing severity of hyperglycemia on mitochondrial stress and mitophagy.A case-control study included healthy controls, subjects with prediabetes, newly diagnosed T2DM (NDT2DM) and advanced duration of T2DM (ADT2DM) (n?=?20 each). Mitochondrial stress indices, transcriptional and translational expression of mitophagy markers (PINK1, PARKIN, MFN2, NIX, LC3-II, and LAMP-2) and transmission electron microscopic (TEM) studies were performed in peripheral blood mononuclear cells.With mild hyperglycemia in subjects with prediabetes, to moderate to severe hyperglycemia in NDT2DM and ADT2DM, a progressive rise in mitochondrial oxidative stress was observed. Prediabetic subjects exhibited significantly increased expression of mitophagy-related markers and showed a positive association with HOMA-?, whereas, patients with NDT2DM and ADT2DM demonstrated decreased expression, with a greater decline in ADT2DM subjects. TEM studies revealed significantly reduced number of distorted mitochondria in prediabetics, as compared to the T2DM patients. In addition, receiver operating characteristic analysis showed HbA1C?>?7% (53?mmol/mol) was associated with attenuated mitophagy.Increasing hyperglycemia is associated with progressive rise in oxidative stress and altered mitochondrial morphology. Sustenance of mitophagy at HbA1C?

SUBMITTER: Bhansali S

PROVIDER: S-EPMC5737033 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with Prediabetes and Type 2 Diabetes Mellitus.

Bhansali Shipra S Bhansali Anil A Walia Rama R Saikia Uma Nahar UN Dhawan Veena V

Frontiers in endocrinology 20171215

<h4>Background and aim</h4>Hyperglycemia-mediated oxidative stress impedes cell-reparative process like autophagy, which has been implicated in impairment of β-cell function in type 2 diabetes mellitus (T2DM). However, the role of mitophagy (selective mitochondrial autophagy) in progression of hyperglycemia remains elusive. This study aimed to assess the impact of increasing severity of hyperglycemia on mitochondrial stress and mitophagy.<h4>Design and methods</h4>A case-control study included h ...[more]

PMID: 29326655

Similar Datasets

Project description: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.

Project description:BackgroundDiabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.MethodsFemale T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.ResultsNo significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.ConclusionBMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

Dataset Information

Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with Prediabetes and Type 2 Diabetes Mellitus.

Publications

Alterations in Mitochondrial Oxidative Stress and Mitophagy in Subjects with Prediabetes and Type 2 Diabetes Mellitus.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets