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Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways

We previously demonstrated that an aspalathin-enriched green rooibos extract (GRE) reversed palmitate-induced insulin resistance in C2C12 skeletal muscle and 3T3-L1 fat cells by modulating key effectors of insulin signalling such as phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI...

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Autores principales: Mazibuko-Mbeje, Sithandiwe E., Dludla, Phiwayinkosi V., Roux, Candice, Johnson, Rabia, Ghoor, Samira, Joubert, Elizabeth, Louw, Johan, Opoku, Andy R., Muller, Christo J. F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387445/
https://www.ncbi.nlm.nih.gov/pubmed/30717198
http://dx.doi.org/10.3390/ijms20030633
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author Mazibuko-Mbeje, Sithandiwe E.
Dludla, Phiwayinkosi V.
Roux, Candice
Johnson, Rabia
Ghoor, Samira
Joubert, Elizabeth
Louw, Johan
Opoku, Andy R.
Muller, Christo J. F.
author_facet Mazibuko-Mbeje, Sithandiwe E.
Dludla, Phiwayinkosi V.
Roux, Candice
Johnson, Rabia
Ghoor, Samira
Joubert, Elizabeth
Louw, Johan
Opoku, Andy R.
Muller, Christo J. F.
author_sort Mazibuko-Mbeje, Sithandiwe E.
collection PubMed
description We previously demonstrated that an aspalathin-enriched green rooibos extract (GRE) reversed palmitate-induced insulin resistance in C2C12 skeletal muscle and 3T3-L1 fat cells by modulating key effectors of insulin signalling such as phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK). However, the effect of GRE on hepatic insulin resistance is unknown. The effects of GRE on lipid-induced hepatic insulin resistance using palmitate-exposed C3A liver cells and obese insulin resistant (OBIR) rats were explored. GRE attenuated the palmitate-induced impairment of glucose and lipid metabolism in treated C3A cells and improved insulin sensitivity in OBIR rats. Mechanistically, GRE treatment significantly increased PI3K/AKT and AMPK phosphorylation while concurrently enhancing glucose transporter 2 expression. These findings were further supported by marked stimulation of genes involved in glucose metabolism, such as insulin receptor (Insr) and insulin receptor substrate 1 and 2 (Irs1 and Irs2), as well as those involved in lipid metabolism, including Forkhead box protein O1 (FOXO1) and carnitine palmitoyl transferase 1 (CPT1) following GRE treatment. GRE showed a strong potential to ameliorate hepatic insulin resistance by improving insulin sensitivity through the regulation of PI3K/AKT, FOXO1 and AMPK-mediated pathways.
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spelling pubmed-63874452019-02-27 Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways Mazibuko-Mbeje, Sithandiwe E. Dludla, Phiwayinkosi V. Roux, Candice Johnson, Rabia Ghoor, Samira Joubert, Elizabeth Louw, Johan Opoku, Andy R. Muller, Christo J. F. Int J Mol Sci Article We previously demonstrated that an aspalathin-enriched green rooibos extract (GRE) reversed palmitate-induced insulin resistance in C2C12 skeletal muscle and 3T3-L1 fat cells by modulating key effectors of insulin signalling such as phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/AKT) and AMP-activated protein kinase (AMPK). However, the effect of GRE on hepatic insulin resistance is unknown. The effects of GRE on lipid-induced hepatic insulin resistance using palmitate-exposed C3A liver cells and obese insulin resistant (OBIR) rats were explored. GRE attenuated the palmitate-induced impairment of glucose and lipid metabolism in treated C3A cells and improved insulin sensitivity in OBIR rats. Mechanistically, GRE treatment significantly increased PI3K/AKT and AMPK phosphorylation while concurrently enhancing glucose transporter 2 expression. These findings were further supported by marked stimulation of genes involved in glucose metabolism, such as insulin receptor (Insr) and insulin receptor substrate 1 and 2 (Irs1 and Irs2), as well as those involved in lipid metabolism, including Forkhead box protein O1 (FOXO1) and carnitine palmitoyl transferase 1 (CPT1) following GRE treatment. GRE showed a strong potential to ameliorate hepatic insulin resistance by improving insulin sensitivity through the regulation of PI3K/AKT, FOXO1 and AMPK-mediated pathways. MDPI 2019-02-01 /pmc/articles/PMC6387445/ /pubmed/30717198 http://dx.doi.org/10.3390/ijms20030633 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mazibuko-Mbeje, Sithandiwe E.
Dludla, Phiwayinkosi V.
Roux, Candice
Johnson, Rabia
Ghoor, Samira
Joubert, Elizabeth
Louw, Johan
Opoku, Andy R.
Muller, Christo J. F.
Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title_full Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title_fullStr Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title_full_unstemmed Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title_short Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways
title_sort aspalathin-enriched green rooibos extract reduces hepatic insulin resistance by modulating pi3k/akt and ampk pathways
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6387445/
https://www.ncbi.nlm.nih.gov/pubmed/30717198
http://dx.doi.org/10.3390/ijms20030633
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