Hesperidin alleviates insulin resistance by improving HG-induced oxidative stress and mitochondrial dysfunction by restoring miR-149
Open Access
- 29 April 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Diabetology & Metabolic Syndrome
- Vol. 13 (1), 1-11
- https://doi.org/10.1186/s13098-021-00664-1
Abstract
Hesperidin, a natural flavanone, has been proven to have multiple protective effects in diabetic rats, such as antioxidant, anti-inflammatory and anti-apoptotic effects. However, the molecular mechanisms underlying the effects of hesperidin are not well elucidated. LO2 cells were stimulated with high glucose (HG, 33 mM) for 24 h to establish a model of oxidative stress. Then, cell viability was determined using the MTT assay. The antioxidant activities, including the reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, mitochondrial membrane potential (MMP) and adenosine-triphosphate (ATP) production, were measured with the corresponding kits. The levels of gene expression, protein expression and methylation were detected using qRT-PCR, western blotting and methylation-specific PCR (MSP) assays, respectively. Compared to the NG treatment, hesperidin treatment increased the viability and improved the oxidative stress, mitochondrial dysfunction and insulin resistance of HG-treated LO2 cells, and these effects were correlated with heightened SOD and GPx activities, increased MMP level and ATP generation, reduced MDA, ROS and glucose levels, and activated GSK3β/AKT and inactivated IRS1 signals. Mechanistically, hesperidin treatment enhanced the miR-149 expression level by reducing its promoter methylation by inhibiting DNMT1. Importantly, knockdown of miR-149 obviously abolished the biological roles of hesperidin. Our findings demonstrated that hesperidin treatment ameliorated HG-induced insulin resistance by reducing oxidative stress and mitochondrial dysfunction partly by suppressing DNMT1-mediated miR-149 silencing.Funding Information
- Heilongjiang Provincial Natural Science Foundation of China (LH2020H080)
- Heilongjiang Postdoctoral Funding Project (LBH-Z19212)
- Heilongjiang University of Traditional Chinese Medicine Research Funding Project (201818, 2019BS02, 2019TD01)
- National Natural Science Foundation of China (82074346)
This publication has 41 references indexed in Scilit:
- Diabetes: a 21st century challengeThe Lancet Diabetes & Endocrinology, 2013
- Hesperetin rescues retinal oxidative stress, neuroinflammation and apoptosis in diabetic ratsMicrovascular Research, 2013
- Methylation-mediated transcriptional repression of microRNAs during cervical carcinogenesisEpigenetics, 2013
- Mitochondrial dysfunction in diabetic cardiomyopathyBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2011
- Oxidative stress, insulin signaling, and diabetesFree Radical Biology & Medicine, 2011
- Mechanisms underlying vascular effect of chronic resveratrol in streptozotocin-diabetic ratsPhytotherapy Research, 2009
- Oxidant stress-induced loss of IRS-1 and IRS-2 proteins in rat skeletal muscle: Role of p38 MAPKFree Radical Biology & Medicine, 2009
- Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mRNA levels in type-2 diabetic miceThe International Journal of Biochemistry & Cell Biology, 2006
- A pancreatic islet-specific microRNA regulates insulin secretionNature, 2004
- Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in DiabetesOnline Journal of Public Health Informatics, 2004