Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells
| Autor: | Fikile T. Mthiyane, Christo J. F. Muller, Khanyisani Ziqubu, Sithandiwe E. Mazibuko-Mbeje, Andani Tshiitamune, Phiwayinkosi V. Dludla, Sinenhlanhla X. H. Mthembu, Ndivhuwo Muvhulawa |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pharmaceutical Science
Gene Expression Organic chemistry Pharmacology Analytical Chemistry Cell Line chemistry.chemical_compound Phosphatidylinositol 3-Kinases Insulin resistance Chalcones QD241-441 Glucosides insulin resistance Drug Discovery energy metabolism medicine Glucose homeostasis Humans Insulin Physical and Theoretical Chemistry Orientin Flavonoids biology Aspalathus Plant Extracts Communication dyslipidemia Glucose transporter medicine.disease IRS1 Insulin receptor Glucose chemistry Diabetes Mellitus Type 2 Liver Chemistry (miscellaneous) biology.protein Hepatocytes Insulin Receptor Substrate Proteins Molecular Medicine GLUT2 palmitate orientin type 2 diabetes Transcriptome Homeostasis Signal Transduction |
| Zdroj: | Molecules, Vol 26, Iss 6154, p 6154 (2021) Molecules |
| ISSN: | 1420-3049 |
| Popis: | Our group has progressively reported on the impact of bioactive compounds found in rooibos (Aspalathus linearis) and their capacity to modulate glucose homeostasis to improve metabolic function in experimental models of type 2 diabetes. In the current study, we investigated how the dietary flavone, orientin, modulates the essential genes involved in energy regulation to enhance substrate metabolism. We used a well-established hepatic insulin resistance model of exposing C3A liver cells to a high concentration of palmitate (0.75 mM) for 16 hrs. These insulin-resistant liver cells were treated with orientin (10 µM) for 3 h to assess the therapeutic effect of orientin. In addition to assessing the rate of metabolic activity, end point measurements assessed include the uptake or utilization of glucose and palmitate, as well as the expression of genes involved in insulin signaling and regulating cellular energy homeostasis. Our results showed that orientin effectively improved metabolic activity, mainly by maintaining substrate utilization which was marked by enhanced glucose and palmitate uptake by liver cells subjected to insulin resistance. Interestingly, these effects can be explained by the improvement in the expression of genes involved in glucose transport (Glut2), insulin signaling (Irs1 and Pi3k), and energy regulation (Ampk and Cpt1). These preliminary findings lay an important foundation for future research to determine the bioactive properties of orientin against dyslipidemia or insulin resistance in reliable and well-established models of type 2 diabetes. |
| Databáze: | OpenAIRE |
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