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

Mazibuko, Sithandiwe E.; Müller, C.; Joubert, Elizabeth; Beer, Dalene de; Johnson, Rabia; Opoku, Andy R.; Louw, Johan

doi:10.1016/j.phymed.2013.03.018

Cited by 81 publications

(83 citation statements)

References 33 publications

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“…In vivo, FFAs induced insulin resistance in skeletal muscle cells with a decrease in ATP generation (44). Rooibos ameliorates palmitate-induced insulin resistance in C2C12 muscle cells with increased cellular ATP levels (45). In support, inhibition of ATP synthase using oligomycin reduces cellular ATP levels and induces insulin resistance in cultured human myotubes (46).…”

Section: Discussionmentioning

confidence: 99%

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

Wang

Chen

et al. 2014

Diabetes

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ATP synthase b subunit (ATPSb) had been previously shown to play an important role in controlling ATP synthesis in pancreatic b-cells. This study aimed to investigate the role of ATPSb in regulation of hepatic ATP content and glucose metabolism in diabetic mice. ATPSb expression and ATP content were both reduced in the livers of type 1 and type 2 diabetic mice. Hepatic overexpression of ATPSb elevated cellular ATP content and ameliorated hyperglycemia of streptozocininduced diabetic mice and db/db mice. ATPSb overexpression increased phosphorylated Akt (pAkt) levels and reduced PEPCK and G6pase expression levels in the livers. Consistently, ATPSb overexpression repressed hepatic glucose production in db/db mice. In cultured hepatocytes, ATPSb overexpression increased intracellular and extracellular ATP content, elevated the cytosolic free calcium level, and activated Akt independent of insulin. The ATPSb-induced increase in cytosolic free calcium and pAkt levels was attenuated by inhibition of P2 receptors. Notably, inhibition of calmodulin (CaM) completely abolished ATPSbinduced Akt activation in liver cells. Inhibition of P2 receptors or CaM blocked ATPSb-induced nuclear exclusion of forkhead box O1 in liver cells. In conclusion, a decrease in hepatic ATPSb expression in the liver, leading to the attenuation of ATP-P2 receptor-CaM-Akt pathway, may play an important role in the progression of diabetes. In past decades, diabetes became one of the major diseases threatening our health, with an estimated global prevalence of 6.4% in 2010 (1). The liver is the key tissue that releases glucose into the circulation in fasting status, and an increase in hepatic glucose production due to insulin deficiency or insulin resistance is the central event in the development and progression of type 1 or type 2 diabetes (2). Moreover, the liver is also one of the key tissues for lipid metabolism.ATP serves as an energy molecule as well as a signal molecule in many cells (3). We previously showed that leucine upregulates the ATP synthase b (ATPSb) subunit to enhance ATP synthesis and insulin secretion in rat islets, type 2 diabetic human islets, and Rattus insulin-1 (INS-1) cells. Overexpression or knockdown of ATPSb increases or reduces cellular ATP levels in INS-1 cells (4,5). Overall, these findings suggest that ATPSb plays a crucial role in controlling ATP synthesis.

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Section: Discussionmentioning

confidence: 99%

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

Wang

Chen

et al. 2014

Diabetes

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“…Xiao et al (2012), reviewing -glucosidase inhibition by various polyphenols, concluded that the C2=C3 double bond of flavonoids is also an important structural feature contributing to enhanced activity compared to compounds with a saturated bond. At a molecular level aspalathin resensitised insulin signalling suppressed by palmitate via protein kinase B (PKB, also known as Akt) and activated the insulin-independent AMPK pathway, culminating in increased glucose uptake via GLUT4 (Mazibuko et al, 2015). Son et al (2013), using L6 myotubes, reported that aspalathin increased glucose uptake by increasing AMPK phosphorylation and GLUT4 translocation to the membrane.…”

Section: Anti-diabetic Propertiesmentioning

confidence: 99%

“…Luteolin was demonstrated to be one of the constituents with moderate PPARγ binding activity (IC 50 = 3.9 µM). Sanderson et al (2014) demonstrated that a fermented rooibos extract suppressed the expression of PPARγ and suppressed adipogenesis in undifferentiated 3T3-L1 cells, while Mazibuko et al (2015) showed that this gene was activated both by rooibos and aspalathin in fully differentiated 3T3-L1 cells. This is an interesting finding in terms of adipogenesis as AMPK and PPARγ play central, yet opposing roles regulating fatty acid synthesis and lipolysis, respectively (Daval et al, 2005).…”

Section: Anti-obesitymentioning

confidence: 99%

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Potential of rooibos, its majorC-glucosyl flavonoids, andZ-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid in prevention of metabolic syndrome

Muller

Malherbe

Chellan

et al. 2017

Critical Reviews in Food Science and Nutrition

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Risk factors of type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) cluster together and are termed the metabolic syndrome. Key factors driving the metabolic syndrome are inflammation, oxidative stress, insulin resistance (IR), and obesity. IR is defined as the impairment of insulin to achieve its physiological effects, resulting in glucose and lipid metabolic dysfunction in tissues such as muscle, fat, kidney, liver, and pancreatic β-cells. The potential of rooibos extract and its major C-glucosyl flavonoids, in particular aspalathin, a C-glucoside dihydrochalcone, as well as the phenolic precursor, Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, to prevent the metabolic syndrome, will be highlighted. The mechanisms whereby these phenolic compounds elicit positive effects on inflammation, cellular oxidative stress and transcription factors that regulate the expression of genes involved in glucose and lipid metabolism will be discussed in terms of their potential in ameliorating features of the metabolic syndrome and the development of serious metabolic disease. An overview of the phenolic composition of rooibos and the changes during processing will provide relevant background on this herbal tea, while a discussion of the bioavailability of the major rooibos C-glucosyl flavonoids will give insight into a key aspect of the bioefficacy of rooibos.

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“…Rooibos ( Aspalathus linearis ) is a plant grown in South Africa that is popularly used in tea and has been shown to activate AMPK 125. Treatment of C2C12 myotubes with rooibos extract increases glucose uptake, mitochondrial activity, GLUT4 expression, and ATP production, and it reverses palmitate-induced IR 125.…”

Section: Ampk Activatorsmentioning

confidence: 99%

AMPK activation: a therapeutic target for type 2 diabetes?

Coughlan¹,

Valentine²,

Ruderman³

et al. 2014

DMSO

219

169

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Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other) tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological) can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones) are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D.

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

Cited by 81 publications

References 33 publications

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

Hepatic Overexpression of ATP Synthase β Subunit Activates PI3K/Akt Pathway to Ameliorate Hyperglycemia of Diabetic Mice

Potential of rooibos, its majorC-glucosyl flavonoids, andZ-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid in prevention of metabolic syndrome

AMPK activation: a therapeutic target for type 2 diabetes?

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