Department of Veterinary Public Health and Food Safety, National Institute of Health, Rome, Italy.
Diabetes. 2011 Sep;60(9):2234-44. doi: 10.2337/db10-1461. Epub 2011 Jul 25.
Insulin resistance (IR) represents an independent risk factor for metabolic, cardiovascular, and neoplastic disorders. Preventing/attenuating IR is a major objective to be reached to preserve population health. Because many insulin-sensitizing drugs have shown unwanted side effects, active harmless compounds are sought after. Dietary anthocyanins have been demonstrated to ameliorate hyperglycemia and insulin sensitivity. This study aimed at investigating whether cyanidin-3-O-β-glucoside (C3G) and its metabolite protocatechuic acid (PCA) might have a role in glucose transport activation in human omental adipocytes and 3T3-L1 cells.
In cells treated with 50 µmol/L C3G and 100 µmol/L PCA, [(3)H]-2-deoxyglucose uptake, GLUT4 translocation by immunoblotting, adiponectin secretion, and peroxisome proliferator-activated receptor-γ (PPARγ) activation by enzyme-linked immunosorbent assay kits were evaluated. Parallel experiments were carried out in murine adipocyte 3T3-L1. To define the role of PPARγ in modulating polyphenol effects, small interfering RNA technique and PPARγ antagonist were used to inhibit transcription factor activity.
C3G and PCA increased adipocyte glucose uptake (P < 0.05) and GLUT4 membrane translocation (P < 0.01). Significant increases (P < 0.05) in nuclear PPARγ activity, as well as in adiponectin and GLUT4 expressions (P < 0.01), were also shown. It is interesting that PPARγ inhibition counteracted the polyphenol-induced adiponectin and GLUT4 upregulations, suggesting a direct involvement of PPARγ in this process.
Our study provides evidence that C3G and PCA might exert insulin-like activities by PPARγ activation, evidencing a causal relationship between this transcription factor and adiponectin and GLUT4 upregulation. Dietary polyphenols could be included in the preventive/therapeutic armory against pathological conditions associated with IR.
胰岛素抵抗（IR）是代谢、心血管和肿瘤疾病的独立危险因素。预防/减轻 IR 是保持人群健康的主要目标。由于许多胰岛素增敏药物显示出不良的副作用，因此正在寻找活性无害的化合物。膳食花色苷已被证明可改善高血糖和胰岛素敏感性。本研究旨在研究矢车菊素-3-O-β-葡萄糖苷（C3G）及其代谢产物原儿茶酸（PCA）是否可能在人网膜脂肪细胞和 3T3-L1 细胞的葡萄糖转运激活中发挥作用。
在用 50µmol/L C3G 和 100µmol/L PCA 处理的细胞中，通过免疫印迹法评估[（3）H]-2-脱氧葡萄糖摄取、GLUT4 易位、脂联素分泌和过氧化物酶体增殖物激活受体-γ（PPARγ）的酶联免疫吸附试剂盒激活。在鼠脂肪细胞 3T3-L1 中进行平行实验。为了确定 PPARγ 在调节多酚作用中的作用，使用小干扰 RNA 技术和 PPARγ 拮抗剂抑制转录因子活性。
C3G 和 PCA 增加了脂肪细胞的葡萄糖摄取（P<0.05）和 GLUT4 膜易位（P<0.01）。还显示核 PPARγ 活性以及脂联素和 GLUT4 表达显著增加（P<0.01）。有趣的是，PPARγ 抑制作用抵消了多酚诱导的脂联素和 GLUT4 上调，表明 PPARγ 直接参与了这一过程。
我们的研究提供了证据表明，C3G 和 PCA 可能通过 PPARγ 激活发挥胰岛素样作用，表明该转录因子与脂联素和 GLUT4 上调之间存在因果关系。膳食多酚可以被纳入预防/治疗与 IR 相关的病理状况的武器库。
