Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.
Tetradecyl 2,3-Dihydroxybenzoate Improves the Symptoms of Diabetic Mice by Modulation of Insulin and Adiponectin Signaling Pathways.
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2,3-二羟基苯甲酸十四酯通过调节胰岛素和脂联素信号通路改善糖尿病小鼠的症状
DOI：
10.3389/fphar.2017.00806
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发表时间：
2017
影响因子：
5.6
通讯作者：
Qi J
中科院分区：
文献类型：
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作者：
Xiang L;Li J;Wang Y;Tang R;Wang Q;Wu Q;Qi J
背景资料：2，3-二羟基苯甲酸十四烷基酯（ABG-001）是一种具有神经生长因子（NGF）模拟作用的先导化合物，可通过IGF-1/PI 3 K/ERK信号通路诱导PC 12细胞突起生长。方法：以2，3-二羟基苯甲酸和十四醇为原料，在一定的反应条件下合成ABG-001。采用链脲佐菌素（STZ）诱导的糖尿病小鼠，观察其抗糖尿病作用。通过口服葡萄糖耐量试验、胰岛素耐量试验、RT-PCR、Western blot、ELISA检测及组织切片等方法分析其作用机制。结果：ABG-001对STZ诱导的糖尿病小鼠有明显的降糖作用。在糖尿病小鼠中，20 mg/kg剂量的ABG-001的抗糖尿病作用与140 mg/kg剂量的二甲双胍相同。此外，糖耐量和胰岛素敏感性显着改善糖尿病小鼠。血浆胰岛素、脂联素和瘦素明显升高，而胰高血糖素明显降低。脂肪组织脂联素和瘦素基因表达明显增加，肝脏和腓肠肌葡萄糖转运蛋白4和脂联素受体1基因表达明显增加，下丘脑和胰腺ADR 2基因表达明显增加。结论：ABG-001通过调节胰岛素和脂联素信号通路发挥抗糖尿病作用。这种新型分子可能是治疗糖尿病的有前途的候选药物。
Background: Tetradecyl 2,3-dihydroxybenzoate (ABG-001) derived from Chinese medicine, gentiana regescens Franch is a leading compound with NGF mimic effect, it can induce neurite outgrowth of PC12 cells via the IGF-1/PI3K/ERK signaling pathway. Thus, we inferred that this compound had anti-diabetic effect and used streptozocin (STZ)-induced diabetic mice to indicate it. Methods: ABG-001 was synthesized with 2,3-dihydroxybenzoic acid and tetradecyl alcohol under certain reaction conditions. STZ-induced diabetic mice were used to investigate anti-diabetic effect. Oral glucose tolerance test, insulin tolerance test, RT-PCR, Western blot, ELISA assays and histological section were performed to do the analysis of action mechanism. Results: ABG-001 showed anti-diabetic effect in STZ-induced diabetic mice. In diabetic mice, the anti-diabetic effect of ABG-001 at a dose of 20 mg/kg was equal with metformin at a dose of 140 mg/kg. Moreover, glucose tolerance and insulin sensitivity were significantly improved on diabetic mice. The plasma insulin, adiponectin and leptin were notably increased, whereas glucagon remarkably decreased. The gene expressions of adiponectin and leptin in adipose tissue, glucose transporter 4 and adiponectin receptor 1 in liver and gastrocnemius, ADR2 in hypothalamus and pancreas were obviously increased. Conclusion: ABG-001 exerts antidiabetic effects via modulation of insulin and adiponectin signaling pathways. This new type of molecule could be a promising drug candidate for treatment of diabetes.
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DOI：
10.1530/joe-13-0339
发表时间：
2014-02
期刊：
The Journal of endocrinology
影响因子：
--
作者：
Cao H
通讯作者：
Cao H
影响因子：
8.9
作者：
Lihn, AS;Pedersen, SB;Richelsen, B
通讯作者：
Richelsen, B
影响因子：
3.6
作者：
Tang, Ruiqi;Gao, Lijuan;Qi, Jianhua
通讯作者：
Qi, Jianhua
影响因子：
2.8
作者：
Ji W;Chen X;Lv J;Wang M;Ren S;Yuan B;Wang B;Chen L
通讯作者：
Chen L
影响因子：
82.9
作者：
通讯作者：
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