Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KK(Ay) mice.
Anti-diabetic effects and mechanisms of action of a Chinese herbal medicine preparation JQ-R in vitro and in diabetic KK(Ay) mice.
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DOI：
10.1016/j.apsb.2017.04.010
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Shen Z
中科院分区：
文献类型：
--
作者：
Liu Q;Liu S;Gao L;Sun S;Huan Y;Li C;Wang Y;Guo N;Shen Z
精制金芪降糖片（JQ-R）是中药复方金芪降糖片的主要原料黄连（毛茛科）、黄芪（豆科）和日本黄芪（忍冬科）的精制提取物的混合物。在2型糖尿病KKAy小鼠和胰岛素抵抗的L 6肌管中研究了JQ-R调节葡萄糖代谢和改善胰岛素敏感性的机制。为了研究JQ-R改善胰岛素敏感性的机制，在L 6肌管中建立了棕榈酸（PA）诱导的胰岛素抵抗细胞模型。免疫印迹法检测葡萄糖摄取和参与胰岛素信号传导、应激和炎症途径的因子的表达。JQ-R在正葡萄糖钳夹实验中显示出对葡萄糖稳态和胰岛素抵抗的有益作用，并降低糖尿病KKAy小鼠的空腹胰岛素水平。JQ-R还改善了血脂谱。JQ-R可直接提高胰岛素抵抗L 6细胞超氧化物歧化酶（SOD）活性，降低丙二醛（MDA）和诱导型一氧化氮合酶（iNOS）水平，并通过上调AKT磷酸化水平，提高胰岛素刺激的葡萄糖摄取。与对照组相比，JQ-R处理后核因子κ B（NF-κB p65）、NF-κB抑制剂（IκB α）、c-Jun N末端激酶（JNK 1/2）和细胞外信号调节激酶（ERK 1/2）的磷酸化水平也发生了变化。这些发现表明JQ-R改善了糖尿病KKAy小鼠的葡萄糖和脂质代谢。JQ-R直接增强胰岛素抵抗肌管中胰岛素刺激的葡萄糖摄取，改善胰岛素信号传导和炎症反应和氧化应激。JQ-R可能是改善2型糖尿病患者糖代谢和胰岛素敏感性的候选药物。金芪降糖片（JQ-R）的三种主要草药的精制提取物的混合物通过经由胰岛素依赖性PI 3 K-AKT通路刺激葡萄糖摄取来改善糖尿病KKAy小鼠和L 6肌管中的葡萄糖代谢。
Refined-JQ (JQ-R) is a mixture of refined extracts from Coptis chinensis (Ranunculaceae), Astragalus membranaceus (Leguminosae) and Lonicera japonica (Caprifoliaceae), the three major herbs of JinQi-JiangTang tablet, a traditional Chinese medicine (TCM) formula. The mechanisms by which JQ-R regulates glucose metabolism and improves insulin sensitivity were studied in type 2 diabetic KKAy mice and insulin-resistant L6 myotubes. To investigate the mechanisms by which JQ-R improves insulin sensitivity, a model of insulin-resistant cells induced with palmitic acid (PA) was established in L6 myotubes. Glucose uptake and expression of factors involved in insulin signaling, stress, and inflammatory pathways were detected by immunoblotting. JQ-R showed beneficial effects on glucose homeostasis and insulin resistance in a euglycemic clamp experiment and decreased fasting insulin levels in diabetic KKAy mice. JQ-R also improved the plasma lipid profiles. JQ-R directly increased the activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) as well as inducible nitric oxide synthase (iNOS) levels in insulin-resistant L6 cells, and elevated the insulin-stimulated glucose uptake with upregulated phosphorylation of AKT. The phosphorylation levels of nuclear factor kappa B (NF-κB p65), inhibitor of NF-κB (IκB α), c-Jun N-terminal kinase (JNK1/2) and extracellular-signal-regulated kinases (ERK1/2) were also changed after JQ-R treatment compared with the control group. Together these findings suggest that JQ-R improved glucose and lipid metabolism in diabetic KKAy mice. JQ-R directly enhanced insulin-stimulated glucose uptake in insulin-resistant myotubes with improved insulin signalling and inflammatory response and oxidative stress. JQ-R could be a candidate to achieve improved glucose metabolism and insulin sensitivity in type 2 diabetes mellitus. A mixture of refined extracts from three major herbs of JinQi-JiangTang tablets (JQ-R) improved glucose metabolism in diabetic KKAy mice and L6 myotubes by stimulating glucose uptake via the insulin-dependent PI3K-AKT pathway.
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