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Morin Exerts Anti-Diabetic Effects in Human HepG2 Cells Via Down-Regulation of miR-29a
Toktam Razavi1, Shideh Montasser Kouhsari1, Khalil Abnous2
1Department of Cellular and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Abstract:
Diabetes mellitus is a complex metabolic disease around the world that is characterized by hyperglycemia resulting from impaired insulin secretion, insulin action, or both. MicroRNA-29a is an important regulator of insulin signaling and gluconeogenesis pathways through IRS2, PI3K and PEPCK expressions which up regulates in Diabetes. Morin is a substantial bioflavonoid which has insulin mimetic effect, and interacting with nucleic acids and proteins. In this study HepG2 cells, were exposed to high glucose to induce diabetic condition. We have determined whether high glucose stimulation might promotes miR-29a expression level in HepG2 cells and subsequently evaluated the Morin treatment effects on this state. In HepG2 cells, high glucose increases miR-29a expression level and decreases its target genes, IRS2 and PI3K expression, and increases associated downstream gene in gluconeogenic pathway, PEPCK. Morin treatment down regulates miR-29a expression level and improves insulin signaling and glucose metabolism. To confirm the inhibitory effects of Morin on miR-29a, we have transfected cells with mimic and inhibitor-miR-29a. This study for the first time identifies that Morin improves diabetic condition through down regulation of the miR-29a level, and suggest that this new inhibitor of miR-29a may be a useful biomedicine to treat diabetes.
Insights
Morin, a bioflavonoid, effectively treats diabetes by down-regulating microRNA-29a (miR-29a) expression. This action improves insulin signaling and glucose metabolism in diabetic conditions.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Diabetes mellitus is a global metabolic disorder characterized by hyperglycemia.
- MicroRNA-29a (miR-29a) plays a key role in regulating insulin signaling and gluconeogenesis.
- Morin, a bioflavonoid, exhibits insulin-mimetic properties.
Purpose of the Study:
- To investigate the effect of high glucose on miR-29a expression in HepG2 cells.
- To evaluate the therapeutic potential of Morin in a high-glucose-induced diabetic model.
- To elucidate the mechanism of Morin's action on miR-29a and related metabolic pathways.
Main Methods:
- HepG2 cells were exposed to high glucose to simulate diabetic conditions.
- miR-29a expression levels were measured using quantitative real-time PCR.
- Expression of target genes (IRS2, PI3K) and gluconeogenic genes (PEPCK) were analyzed.
- Cells were treated with Morin, and transfections with miR-29a mimic/inhibitor were performed.
Main Results:
- High glucose significantly increased miR-29a expression in HepG2 cells.
- High glucose decreased IRS2 and PI3K expression while increasing PEPCK expression.
- Morin treatment down-regulated miR-29a, restored IRS2 and PI3K levels, and improved glucose metabolism.
- Transfection studies confirmed Morin's inhibitory effect on miR-29a.
Conclusions:
- Morin effectively ameliorates high-glucose-induced diabetic conditions in HepG2 cells.
- The therapeutic effect of Morin is mediated through the down-regulation of miR-29a.
- Morin represents a potential novel therapeutic agent for diabetes treatment by targeting miR-29a.
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