Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells.
Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells.
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DOI：
10.3389/fphar.2021.656220
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发表时间：
2021
影响因子：
5.6
通讯作者：
Nan JX
中科院分区：
文献类型：
--
作者：
Bao S;Wang X;Cho SB;Wu YL;Wei C;Han S;Bao L;Wu Q;Ao W;Nan JX
我们先前已经报道，沙参寡糖通过增加肝组织中胰岛素受体(INS-R)、胰岛素受体底物-2(IRS-2)、磷脂酰肌醇3激酶(PI3K)、蛋白激酶B(AKT)、过氧化物酶体增殖物激活受体(PPAR)-γ和葡萄糖转运蛋白4(GLUT4)蛋白的激活而显著增强血糖控制。然而，AOS控制血糖对db/db小鼠和MIN6细胞的胰腺组织的调节作用仍有待确定。给2型糖尿病db/db小鼠口服AOS(380或750 mg/kg)8周，以确定AOS是否通过INS-R/IRS/GLUT4介导的胰岛素途径调节血糖。同时，还研究了AOS对MIN6细胞葡萄糖摄取及其相关信号通路的影响。结果表明，AOS治疗组大鼠随机血糖(RBG)水平明显低于对照组。AOS能降低db/db小鼠糖化血红蛋白(HbA1c)和游离脂肪酸(FFA)水平，明显改善胰腺组织的病理变化。免疫组织化学分析显示，AOS治疗组INS-R、IRS-1、IRS-2和GLUT4的表达均高于模型组。此外，用MIN6细胞进行的体外实验表明，AOS调节INS-R、IRS-1、IRS-2和GLUT4的蛋白和mRNA水平，并减轻胰岛素抵抗和细胞凋亡。体外和体内实验结果具有可比性。3-氨基-9-乙基咔唑(AEC)柱前衍生化AOS的超高效液相色谱-飞行时间质谱仪初步鉴定了5种糖：葡萄糖、乳糖、芦丁糖、葡萄糖醛酸和麦芽三糖。我们目前的研究清楚地表明，AOS可以有效地预防高血糖，可能是通过调节Ins-R/IRS/GLUT4胰岛素信号通路来提高胰岛素敏感性和改善IR。因此，AOS可能被认为是一种潜在的治疗糖尿病的药物。
We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.
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DOI：
10.3390/molecules20022786
发表时间：
2015-02-09
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Chang WC;Wu SC;Xu KD;Liao BC;Wu JF;Cheng AS
通讯作者：
Cheng AS
DOI：
10.1016/j.ijbiomac.2019.11.031
发表时间：
2020-07-01
影响因子：
8.2
作者：
Abdel-Moneim, Adel;El-Shahawy, Ahmed;Taha, Mohamed
通讯作者：
Taha, Mohamed
影响因子：
5.1
作者：
Cho, N. H.;Shaw, J. E.;Malanda, B.
通讯作者：
Malanda, B.
影响因子：
--
作者：
Bao Shu-yin;Han Shu-ying;Ao Wu-liji
通讯作者：
Ao Wu-liji
IRS信号传导降低会损害β细胞周期的进程和过表达β细胞S6K的转基因小鼠的存活。
影响因子：
7.7
作者：
Elghazi L;Balcazar N;Blandino-Rosano M;Cras-Méneur C;Fatrai S;Gould AP;Chi MM;Moley KH;Bernal-Mizrachi E
通讯作者：
Bernal-Mizrachi E