Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance
Effects of a grapeseed procyanidin extract (GSPE) on insulin resistance
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DOI：
10.1016/j.jnutbio.2009.08.001
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发表时间：
2010-10-01
影响因子：
5.6
通讯作者：
Ardevol, Anna
中科院分区：
文献类型：
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作者：
Montagut, Gemma;Blade, Cinta;Ardevol, Anna
黄酮类化合物是对抗代谢综合征危险因素的有益化合物，但其对葡萄糖稳态调节的作用和机制尚不清楚。在本研究中，我们首先检查了葡萄藤原花青素提取物（GSPE）刺激胰岛素抵抗3 T3-L1脂肪细胞葡萄糖摄取的功效。结果表明，当慢性胰岛素治疗诱导抵抗时，GSPE保持比胰岛素更高的刺激能力。相比之下，当地塞米松用作耐药诱导剂时，GSPE的效果较差。接下来，我们评估了不同的GSPE治疗在改善高胰岛素血症动物（喂食自助餐饮食）中的葡萄糖代谢方面的有效性。GSPE降低血浆胰岛素水平。较低剂量（25 mg GSPE/kg体重/天）给药30天改善稳态模型评估-胰岛素抵抗指数。这伴随着肠系膜白色脂肪组织中Pparg 2、Glut 4和Irs 1的下调。类似地，胰岛素抵抗的3 T3-L1脂肪细胞的慢性GSPE处理下调了那些脂肪细胞标志物的mRNA水平，尽管细胞仍然能够对葡萄糖摄取的急性刺激做出响应。总之，25 mg/kg体重/天的GSPE对葡萄糖稳态具有积极的长期影响，并且GSPE可以靶向脂肪组织，在那里它可能直接刺激葡萄糖摄取。这项工作还强调需要仔细考虑生物活性剂量，因为更高的剂量不一定与更大的积极作用相关。(C)2010年爱思唯尔公司All rights reserved.
Flavonoids are beneficial compounds against risk factors for metabolic syndrome, but their effects and the mechanisms on glucose homeostasis modulation are not well defined. In the present study, we first checked the efficacy of grapeseed procyanidin extract (GSPE) for stimulating glucose uptake in insulin-resistant 3T3-L1 adipocytes. Results show that when resistance is induced with chronic insulin treatment, GSPE maintain a higher stimulating capacity than insulin. In contrast, when dexamethasone is used as the resistance-inducing agent, GSPE is less effective. Next we evaluated how effective different GSPE treatments are at improving glucose metabolism in hyperinsulinemic animals (fed a cafeteria diet). GSPE reduced plasma insulin levels. The lower dose (25 mg GSPE/kg body weight per day) administered for 30 days improved the HOmeostasis Model Assessment-insulin resistance index. This was accompanied by down-regulation of Pparg2, Glut4 and Irs1 in mesenteric white adipose tissue. Similarly, a chronic GSPE treatment of insulin-resistant 3T3-L1 adipocytes down-regulated the mRNA levels of those adipocyte markers, although cells were still able to respond to the acute stimulation of glucose uptake.In summary, 25 mg/kg body weight per day of GSPE has a positive long-term effect on glucose homeostasis, and GSPE could be targeted at adipose tissue, where it might directly stimulate glucose uptake. This work also highlights the need to carefully consider the bioactive dose, since a higher dose does not necessarily correlate to a greater positive effect. (C) 2010 Elsevier Inc. All rights reserved.