Amelioration of palmitate-induced insulin resistance in C2C12 muscle cells by rooibos (Aspalathus linearis)

Increased levels of free fatty acids (FFAs), specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle, fat and liver. Skeletal muscle, responsible for up to 80% of the glucose disposal from the peripheral circulation, is particularly vulnerable to in...

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Published in:	Phytomedicine (Stuttgart) Vol. 20; no. 10; pp. 813 - 819
Main Authors:	Mazibuko, S.E., Muller, C.J.F., Joubert, E., de Beer, D., Johnson, R., Opoku, A.R., Louw, J.
Format:	Journal Article
Language:	English
Published:	Germany Elsevier GmbH 15-07-2013 Urban & Fischer Verlag
Subjects:	Animals Aspalathin Aspalathus - chemistry Aspalathus linearis Beans Cell Line Glucose uptake Health aspects Hyperinsulinism - chemically induced Hyperinsulinism - drug therapy Insulin resistance Insulin Resistance - physiology Legumes Medicinal plants Mice Mimosaceae Muscle cells Muscle, Skeletal - cytology Muscle, Skeletal - drug effects Muscle, Skeletal - enzymology Palmitate Palmitic Acid - pharmacology Palmitic Acid - therapeutic use Physiological aspects Phytotherapy Plant Extracts - pharmacology Plant Extracts - therapeutic use Rooibos South Africa tAKT IRS1 IgG pAKT PKC θ HPR MTT DMEM BSA Glucose uptake Aspalathus linearis Rooibos tAMPK pAMPK HPLC-DAD Palmitate T2D TBST IR AKT DAG Aspalathin RNAse tPKC θ FFAs PMSF FCS FRE Insulin resistance AMPK pPKC θ GRE GLUT4 ATP DPBS fermented rooibos extract horseradish peroxidise phenylmethanesulfonylfluoride protein kinase C theta Tris-buffered saline with Tween ribonuclease phosphorylated protein kinase total protein kinase B Dulbecco's Modified Eagle Medium phosphorylated 5′ adenosine monophosphate-activated protein kinase 5′ adenosine monophosphate-activated protein kinase bovine serum albumin diacylglycerol 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide phosphorylated protein kinase C theta total protein kinase C theta Dulbecco's phosphate buffered saline free fatty acids aspalathin-enriched green rooibos extract fetal calf serum glucose transporter type 4 protein kinase B immunoglobulin G high-performance liquid chromatography with diode-array detection total 5′ adenosine monophosphate-activated protein kinase insulin receptor substrate 1 type 2 diabetes adenosine triphosphate
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Summary:	Increased levels of free fatty acids (FFAs), specifically saturated free fatty acids such as palmitate are associated with insulin resistance of muscle, fat and liver. Skeletal muscle, responsible for up to 80% of the glucose disposal from the peripheral circulation, is particularly vulnerable to increased levels of saturated FFAs. Rooibos (Aspalathus linearis) and its unique dihydrochalcone C-glucoside, aspalathin, shown to reduce hyperglycemia in diabetic rats, could play a role in preventing or ameliorating the development of insulin resistance. This study aims to establish whether rooibos can ameliorate experimentally-induced insulin-resistance in C2C12 skeletal muscle cells. Palmitate-induced insulin resistant C2C12 cells were treated with an aspalathin-enriched green (unfermented) rooibos extract (GRE), previously shown for its blood glucose lowering effect in vitro and in vivo or an aqueous extract of fermented rooibos (FRE). Glucose uptake and mitochondrial activity were measured using 2-deoxy-[3H]-d-glucose, MTT and ATP assays, respectively. Expression of proteins relevant to glucose metabolism was analysed by Western blot. GRE contained higher levels of all compounds, except the enolic phenylpyruvic acid-2-O-glucoside and luteolin-7-O-glucoside. Both rooibos extracts increased glucose uptake, mitochondrial activity and ATP production. Compared to FRE, GRE was more effective at increasing glucose uptake and ATP production. At a mechanistic level both extracts down-regulated PKC θ activation, which is associated with palmitate-induced insulin resistance. Furthermore, the extracts increased activation of key regulatory proteins (AKT and AMPK) involved in insulin-dependent and non-insulin regulated signalling pathways. Protein levels of the glucose transporter (GLUT4) involved in glucose transport via these two pathways were also increased. This in vitro study therefore confirms that rooibos can ameliorate palmitate-induced insulin resistance in C2C12 skeletal muscle cells. Inhibition of PKC θ activation and increased activation of AMPK and AKT offer a plausible mechanistic explanation for this ameliorative effect.
Bibliography:	http://dx.doi.org/10.1016/j.phymed.2013.03.018 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0944-7113 1618-095X
DOI:	10.1016/j.phymed.2013.03.018