Opposite Effects of Quercetin, Luteolin, and Epigallocatechin Gallate on Insulin Sensitivity Under Normal and Inflammatory Conditions in Mice
Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009, People's Republic of China. Inflammation
(Impact Factor: 2.21).
07/2012; 36(1). DOI: 10.1007/s10753-012-9514-x
Flavonoids are polyphenolic compounds ubiquitous in plants. Quercetin, luteolin, and epigallocatechin gallate (EGCG) are flavonoids with a number of biochemical and cellular actions relevant to glucose homeostasis, but their regulation of insulin action is still uncertain. This study aims to evaluate the regulation of insulin action by quercetin, luteolin, and EGCG under normal and inflammatory conditions in mice. Oral administration of quercetin, luteolin, and EGCG impaired glucose tolerance and blunted the effect of insulin to low blood glucose. Luteolin and EGCG, but not quercetin, inhibited glucose load-induced insulin receptor substrate-1(IRS-1) tyrosine and Akt phosphorylation in adipose tissue. Meanwhile, insulin-stimulated glucose uptake was also inhibited by these flavonoids. We induced insulin resistance in mice by treatment with activated macrophages-derived conditioned medium (Mac-CM) and observed that quercetin, luteolin, and EGCG reversed glucose intolerance with improving insulin sensitivity. Quercetin, luteolin, and EGCG inhibited inflammation-evoked IKKβ activation and IRS-1 serine phosphorylation in adipose tissue, and thereby effectively restored glucose load-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to an increase in insulin-mediated glucose uptake in adipocytes. The aforementioned results showed opposite effects of quercetin, luteolin, and EGCG on insulin sensitivity in mice. The different modulation of IRS-1 function by phosphorylating modification under normal and inflammatory conditions should be a key controlling for their action in regulation of insulin sensitivity.
Available from: Shengzuo Fang
- "and Bg120 referred to the blood glucose concentration at 0, 30, 60 and 120 min after glucose load) (Shao et al., 2013). "
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ABSTRACT: Cyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine.
The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice.
Mice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500mg/kg, ig.) or metformin (200mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement.
CPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions.
Above-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice.
Journal of ethnopharmacology 02/2014; 153(2). DOI:10.1016/j.jep.2014.02.003 · 3.00 Impact Factor
Available from: Mohammad Abdollahi
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ABSTRACT: Despite the current existence and availability of synthetic drugs for the treatment of diabetes mellitus (DM), these medications are neither cheap nor completely effective. Furthermore, the long-term consumption of synthetic drugs may cause adverse effects, while those medications provided from natural sources are more affordable and have shown lesser adverse effects. The current belief is that oxidative stress plays a substantial role in the pathogenesis of diabetes and its complications. The characteristics of DM as a multifactorial disease are related to a deficit in the β-cells of the pancreas that results in defective production and release of insulin. Antioxidant therapy can protect β-cells from apoptosis and preserve their function. Therefore, the higher the antioxidant effects a compound might have, the higher the positive effects in diabetes anticipated. Our idea is that a combination of strong antioxidants might positively work in control of hyperglycemia by activating the production and release of insulin to the blood. In this scenario, if the strongest multi-herbal antioxidant complex called Setarud (IMOD™) is combined with curcumin and quercetin, then much stronger antioxidant activity with positive effects in the control of diabetes would be produced. To prove the idea, this combination has to be pharmaceutically prepared and then its safety and efficacy must be examined in preclinical and clinical studies.
Iranian Journal of Medical Hypotheses and Ideas 01/2013; 7(1):25–30. DOI:10.1016/j.jmhi.2012.12.002
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ABSTRACT: In this study, we investigated the improvement of fucosylated chondroitin sulfate (CHS) from the cucumber Acaudina molpadioides on hyperglycemia in skeletal muscle of insulin resistant mice. CHS, rosiglitazone (RSG), and their combinations were supplemented to high-fat high-sucrose diet (HFSD)-fed C57BL/6J mice for 19 weeks. The results showed that CHS treatment remarkably decreased blood glucose level and insulin resistance. The glucose metabolism-related genes expressions at the transcriptional level were apparently increased in skeletal muscle. Although the total protein expressions of IR-β, IRS-1, PI3K, PKB and GLUT4 in skeletal muscle were not affected, insulin-stimulated GLUT4 translocation and phosphorylation of Tyr-IR-β, Tyr612-IRS-1, p85-PI3K, Ser473-PKB, and Thr308-PKB were significantly increased by CHS supplement. Additionally, combination of CHS and RSG produced synergistic effects on anti-hyperglycemia. These results indicate that CHS can alleviate hyperglycemia via activation of the PKB/GLUT4 signaling pathway in skeletal muscle of insulin resistant mice.
09/2013; 4(11). DOI:10.1039/c3fo60247h
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