Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine.

Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine.
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小檗碱通过肠道中的 GnRH-GLP-1 和 MAPK 途径调节葡萄糖代谢

DOI:
10.1186/1472-6882-14-188
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发表时间:
2014-06-09
影响因子:
--
通讯作者:
Zheng J
Zheng J
中科院分区:
医学3区
文献类型:
--
作者:
Zhang Q;Xiao X;Li M;Li W;Yu M;Zhang H;Ping F;Wang Z;Zheng J

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众所周知,黄连素可以改善葡萄糖和脂肪代谢紊乱,但它很难从肠道吸收到血液中。因此,黄连素的确切作用机制仍不清楚。在这项研究中,我们研究了黄连素对糖尿病大鼠糖代谢的影响,并验证了黄连素直接作用于末端回肠的假设。将大鼠分为正常对照组、糖尿病组(DM)、黄连素低剂量组(BERL)和黄连素高剂量组(BERH)。回肠组织标本采用罗氏NimbleGen基因芯片、定量聚合酶链式反应和免疫组织化学方法进行分析。我们发现,8周的黄连素治疗显著降低了空腹血糖水平。口服葡萄糖耐量试验(OGTT)显示,BERL和BERH组在口服葡萄糖前和口服葡萄糖后30min、60min和120min时血糖均显著降低。黄连素治疗组餐后血浆胰高血糖素样肽-1(GLP-1)水平升高。BERH组回肠有2112个基因表达发生显著变化(780个增加,1332个减少)。KEGG通路分析表明,所有差异表达基因包括9条KEGG通路。排在前两位的是MAPK信号通路和GnRH信号通路。Q-RT-PCR和免疫组织化学证实BERH组GLP1R和MAPK10表达上调,促性腺激素释放激素受体(GnRHr)和GnRH1表达下调。我们的数据表明,黄连素可以改善糖尿病大鼠的血糖水平。其机制可能与回肠中的MAPK和GnRH-GLP-1通路有关。
Berberine is known to improve glucose and lipid metabolism disorders, but it poorly absorbed into the blood stream from the gut. Therefore, the exact underlying mechanism for berberine is still unknown. In this study, we investigated the effect of berberine on glucose metabolism in diabetic rats and tested the hypothesis that berberine acts directly in the terminal ileums. Rats were divided into a control group, diabetic group (DM), low dose of berberine group (BerL) and high dose of berberine group (BerH). Ileum samples were analyzed using a Roche NimbleGen mRNA array, qPCR and immunohistochemistry. We found that 8 weeks of treatment with berberine significantly decreased fasting blood glucose levels. An oral glucose tolerance test (OGTT) showed that blood glucose was significantly reduced in the BerL and BerH groups before and at 30 min, 60 min and 120 min after oral glucose administration. Plasma postprandial glucagon-like peptide-1 (GLP-1) levels were increased in the berberine-treated groups. The ileum from the BerH group had 2112 genes with significantly changed expression (780 increased, 1332 decreased). KEGG pathway analyses indicated that all differentially expressed genes included 9 KEGG pathways. The top two pathways were the MAPK signaling pathway and the GnRH signaling pathway. Q-RT-PCR and immunohistochemistry verified that glucagon-like peptide 1 receptor (Glp1r) and mitogen activated protein kinase 10 (Mapk10) were significantly up-regulated, in contrast, gonadotropin releasing hormone receptor (Gnrhr) and gonadotropin-releasing hormone 1 (Gnrh1) were down-regulated in the BerH group. Our data suggest that berberine can improve blood glucose levels in diabetic rats. The mechanisms involved may be in the MAPK and GnRh-Glp-1 pathways in the ileum.
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