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Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways.
Int J Mol Sci 2019; 20(3)IJ

Abstract

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.

Authors+Show Affiliations

Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. sithandiwe.mazibuko@mrc.ac.za. Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Private Bag X1, Tygerberg 7505, South Africa. sithandiwe.mazibuko@mrc.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. pdludla@mrc.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. candice.roux@mrc.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. rabia.johnson@mrc.ac.za. Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Private Bag X1, Tygerberg 7505, South Africa. rabia.johnson@mrc.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. samira.ghoor@mrc.ac.za.Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Private Bag X5026, Stellenbosch 7599, South Africa. JoubertL@agric.ac.za. Department of Food Science, Stellenbosch University, Private Bag X1, Matieland 7602, South Africa. JoubertL@agric.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. johan.louw@mrc.ac.za. Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, South Africa. johan.louw@mrc.ac.za.Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, South Africa. opokuA@unizul.ac.za.Biomedical Research and Innovation Platform, South African Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa. christo.muller@mrc.ac.za. Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Private Bag X1, Tygerberg 7505, South Africa. christo.muller@mrc.ac.za. Department of Biochemistry and Microbiology, University of Zululand, Private Bag X1001, KwaDlangezwa 3886, South Africa. christo.muller@mrc.ac.za.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30717198

Citation

Mazibuko-Mbeje, Sithandiwe E., et al. "Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance By Modulating PI3K/AKT and AMPK Pathways." International Journal of Molecular Sciences, vol. 20, no. 3, 2019.
Mazibuko-Mbeje SE, Dludla PV, Roux C, et al. Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways. Int J Mol Sci. 2019;20(3).
Mazibuko-Mbeje, S. E., Dludla, P. V., Roux, C., Johnson, R., Ghoor, S., Joubert, E., ... Muller, C. J. F. (2019). Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways. International Journal of Molecular Sciences, 20(3), doi:10.3390/ijms20030633.
Mazibuko-Mbeje SE, et al. Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance By Modulating PI3K/AKT and AMPK Pathways. Int J Mol Sci. 2019 Feb 1;20(3) PubMed PMID: 30717198.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aspalathin-Enriched Green Rooibos Extract Reduces Hepatic Insulin Resistance by Modulating PI3K/AKT and AMPK Pathways. AU - Mazibuko-Mbeje,Sithandiwe E, AU - Dludla,Phiwayinkosi V, AU - Roux,Candice, AU - Johnson,Rabia, AU - Ghoor,Samira, AU - Joubert,Elizabeth, AU - Louw,Johan, AU - Opoku,Andy R, AU - Muller,Christo J F, Y1 - 2019/02/01/ PY - 2019/01/19/received PY - 2019/01/26/accepted PY - 2019/2/6/entrez PY - 2019/2/6/pubmed PY - 2019/5/18/medline KW - AKT KW - AMPK KW - PI3K KW - diabetes mellitus KW - green rooibos extract KW - insulin resistance KW - metabolic syndrome KW - obesity KW - therapeutic target JF - International journal of molecular sciences JO - Int J Mol Sci VL - 20 IS - 3 N2 - 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. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/30717198/Aspalathin_Enriched_Green_Rooibos_Extract_Reduces_Hepatic_Insulin_Resistance_by_Modulating_PI3K/AKT_and_AMPK_Pathways_ L2 - http://www.mdpi.com/resolver?pii=ijms20030633 DB - PRIME DP - Unbound Medicine ER -