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首页> 外文学位 >Etude des proprietes antidiabetiques de Nigella sativa: Sites d'action cellulaires et moleculaires.
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Etude des proprietes antidiabetiques de Nigella sativa: Sites d'action cellulaires et moleculaires.

机译：Nigella sativa的抗糖尿病特性研究：作用的细胞和分子部位。

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摘要

Nigella sativa or black cumin is a medicinal plant and a popular condiment. The seeds of N. sativa are widely used in the traditional medicine of North African countries for the treatment of diabetes. However, the cellular and molecular mechanisms of action through which the plant exerts its hypoglycemic effect remain unclear. The aim of our study is to determine the effect of N. sativa on insulin secretion, glucose transport and signaling pathways involved in the regulation of glucose homeostasis and metabolism. We carried out in vitro murine cell-based bioassays (betaTC pancreatic beta cells, C2C12 myoblasts, H4IIE hepatocytes and 3T3-L1 adipocytes) and in vivo studies in normoglycemic rats and diabetic Meriones shawi (rodent).;In conclusion, N. sativa has an insulinotropic effect on pancreatic beta cells. Our study has revealed for the first time that N. sativa exerts its antidiabetic activity by a combination of insulino-mimetic and insulin-sensitizing effects, thereby increasing glucose uptake in peripheral tissues. This effect of N. sativa is linked to the stimulation of insulin-dependent and -independent (AMPK) pathway in skeletal muscle and liver, while in adipose tissue, the effect was attributed to the activation of PPARalpha. Finally, the in vivo study confirms the antidiabetic and antihyperlipidemic effects of N. sativa. Our original contribution lies in the demonstration that the in vivo antidiabetic action of N. sativa is exerted though the same mechanisms identified by our in vitro studies. These data support the soundness of the ethnobotanical use of this plant for the treatment of diabetes and its associated dyslipidemia. Moreover, the pleiotropic actions of N. sativa make it a very promising alternative or complementary treatment for diabetes, which calls for immediate high quality clinical trials.;In pancreatic beta cells, N. sativa increased cell proliferation as well as basal and glucose stimulated insulin secretion. It also enhanced glucose uptake in muscle cells by 50%. Moreover, the increase of glucose uptake in fat cells reached levels up to 400%. The experiments using Western immunoblot analysis showed that N. sativa stimulated insulin-dependent (Akt and ERK) as well as -independent (AMPK) pathways in C2C12 cells. In 3T3-L1 cells, the increase of glucose uptake was attributed to the activation of the peroxisome proliferator activated receptor gamma (PPARgamma) pathway. Similarly to C2C12 cells, N. sativa activated Akt and 5' adenosine monophosphate-activated protein kinase (AMPK) in hepatocytes. This activation of AMPK was associated with an uncoupling effect on mitochondrial oxidative phosphorylation. In diabetic Meriones, N. sativa gradually decreased fasting blood glucose and the glycemic response to an oral glucose load (OGTT) to values similar to normal animals at the end of treatment. Improved lipid profile is observed in both animal models. At the molecular level, N. sativa increased muscle glucose transporter 4 (Glut4) content and acetyl-coenzyme A carboxylase (ACC) phosphorylation in soleus muscle and liver in diabetic Meriones shawi. In normal rats, the plant extract induced a stimulation of insulin signaling pathways (Akt and ERK) in the liver.
机译：苜蓿或黑小茴香是药用植物，是一种受欢迎的调味品。苜蓿的种子被广泛用于北非国家的传统医学中，用于治疗糖尿病。然而，尚不清楚植物通过其发挥降血糖作用的细胞和分子作用机理。我们研究的目的是确定紫花苜蓿对参与调节胰岛素稳态和代谢的胰岛素分泌，葡萄糖转运和信号通路的影响。我们进行了基于鼠类细胞的体外生物测定（betaTC胰腺β细胞，C2C12成肌细胞，H4IIE肝细胞和3T3-L1脂肪细胞），并在正常血糖大鼠和糖尿病性Meriones shawi（啮齿动物）中进行了体内研究。对胰腺β细胞有促胰岛素作用。我们的研究首次揭示了紫花苜蓿通过模拟胰岛素和胰岛素增敏作用的结合发挥其抗糖尿病活性，从而增加了周围组织的葡萄糖吸收。紫花苜蓿的这种作用与骨骼肌和肝脏中胰岛素依赖性和非依赖性（AMPK）途径的刺激有关，而在脂肪组织中，该作用归因于PPARalpha的激活。最后，体内研究证实了苜蓿猪笼草的抗糖尿病和抗高血脂作用。我们最初的贡献在于证明，尽管我们的体外研究确定了相同的机制，但紫花苜蓿在体内具有抗糖尿病作用。这些数据支持该植物在植物学上用于治疗糖尿病及其相关血脂异常的正确性。此外，紫花苜蓿的多效性作用使其成为糖尿病的非常有希望的替代疗法或补充疗法，这需要立即进行高质量的临床试验。在胰腺β细胞中，紫花苜蓿可增加细胞增殖以及基础和葡萄糖刺激的胰岛素分泌。它还使肌肉细胞中的葡萄糖摄取增加了50％。此外，脂肪细胞中葡萄糖摄取的增加达到高达400％的水平。使用Western免疫印迹分析的实验表明，紫花苜蓿刺激C2C12细胞中的胰岛素依赖性（Akt和ERK）以及非依赖性（AMPK）途径。在3T3-L1细胞中，葡萄糖摄取的增加归因于过氧化物酶体增殖物激活受体γ（PPARgamma）途径的激活。与C2C12细胞相似，紫花苜蓿激活肝细胞中的Akt和5'腺苷单磷酸激活的蛋白激酶（AMPK）。 AMPK的这种激活与线粒体氧化磷酸化的解偶联作用有关。在糖尿病性鱼尾藻中，紫花苜蓿逐渐降低空腹血糖和对口服葡萄糖负荷（OGTT）的血糖反应，使其达到与治疗结束时正常动物相似的值。在两种动物模型中均观察到改善的脂质分布。在分子水平上，紫花苜蓿增加比目鱼Mewiles shawi的比目鱼肌和肝脏中的肌肉葡萄糖转运蛋白4（Glut4）含量和乙酰辅酶A羧化酶（ACC）磷酸化。在正常大鼠中，植物提取物可刺激肝脏中的胰岛素信号传导途径（Akt和ERK）。

著录项

  • 作者

    Benhaddou Andaloussi, Ali.;

  • 作者单位

    Universite de Montreal (Canada).;

  • 授予单位 Universite de Montreal (Canada).;
  • 学科 Health Sciences Pharmacology.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 270 p.
  • 总页数 270
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 肿瘤学;
  • 关键词

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