Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes.

Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes.
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DOI:
10.1186/s12967-015-0412-5
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发表时间:
2015-02-15
影响因子:
7.4
通讯作者:
Rhyu DY
Rhyu DY
中科院分区:
医学2区
文献类型:
--
作者:
Sharma BR;Kim HJ;Rhyu DY

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胰岛素敏感组织中的PI 3 K/AKT和AMPK途径的缺陷使葡萄糖稳态被扭曲,从而允许葡萄糖在血液中积累。本研究旨在探讨狭叶蕨藻乙醇提取物(CLE)对C57 BL/KsJ-db/db(db/db)小鼠糖代谢的调节作用及其机制。给小鼠施用CLE(250或500 mg/kg BW)或罗格列酮(RSG,10 mg/kg BW)6周。然后进行口服葡萄糖耐量试验(OGTT)和腹腔胰岛素耐量试验(IPITT),并测定db/db小鼠的血糖。在db/db小鼠中测量血浆中胰岛素和胰岛素抵抗因子的水平、肝脏中糖原含量以及骨骼肌中IRS、PI 3 K、AKT和GLUT 4的表达。采用荧光法和蛋白质印迹法测定L 6肌细胞的葡萄糖摄取和胰岛素信号分子。CLE能显著降低db/db小鼠空腹血糖、OGTT和IPITT血糖、血浆胰岛素、胰岛素抵抗指数(HOMA-IR)、TNF-α、IL-6、FFA、TG和TC水平及肝糖原含量。CLE显著增加IRS、AKT、PI 3 K和GLUT 4的活化,这些是db/db小鼠的L 6肌细胞和骨骼肌中PI 3 K/AKT通路的关键效应分子。在L 6肌细胞中,通过用PI 3 K抑制剂(LY 294002)处理而不是通过AMPK抑制剂(化合物C)消除CLE增强的葡萄糖摄取。CLE分别通过PI 3 K/AKT途径调节肌细胞和db/db小鼠的葡萄糖摄取和稳态。我们的结果表明CLE可能是预防糖尿病的潜在候选药物。
Glucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. The purpose of this study was to assess the effects and mechanisms by which ethanol extract of Caulerpa lentillifera (CLE) regulates glucose metabolism in C57BL/KsJ-db/db (db/db) mice. Mice were administered CLE (250 or 500 mg/kg BW) or rosiglitazone (RSG, 10 mg/kg BW) for 6 weeks. Then, oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were performed, and blood glucose was measured in db/db mice. Levels of insulin and insulin resistance factors in plasma, glycogen content in the liver, and IRS, PI3K, AKT, and GLUT4 expressions in skeletal muscles were measured in db/db mice. Glucose uptake and insulin signaling molecules were measured in L6 myocytes, using fluorometry and Western blotting. CLE significantly decreased fasting blood glucose, glucose level in OGTT and IPITT, plasma insulin, homeostatic model assessment-insulin resistant (HOMA-IR), TNF-α, IL-6, FFA, TG and TC levels, and hepatic glycogen content in db/db mice. CLE significantly increased the activation of IRS, AKT, PI3K, and GLUT4, which are the key effector molecules of the PI3K/AKT pathway in L6 myocytes and the skeletal muscles of db/db mice. The enhanced glucose uptake by CLE was abolished by treatment with a PI3K inhibitor (LY294002), but not by an AMPK inhibitor (compound C) in L6 myocytes. CLE regulated glucose uptake and homeostasis via the PI3K/AKT pathway in myocytes and db/db mice, respectively. Our results suggest that CLE could be a potential candidate for the prevention of diabetes.
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