姜黄素对2 型糖尿病大鼠脂肪细胞葡萄糖转运及PI3K/ Akt 信号通路的影响
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(1. 武汉职业技术学院生物工程学院,武汉 430074;2. 湖北省中医院针灸科,武汉 430061)

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R-33


Effect of curcumin on glucose transport and PI3K / Akt signaling pathway in adipocytes of type 2 diabetes mellitus rats
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Affiliation:

(1. School of Biological Engineering, Wuhan Polytechnic, Wuhan 430074, China.2. Department of Acupuncture, Hospital of Traditional Chinese Medical in Hubei, Wuhan 430061)

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    摘要:

    目的 探究姜黄素对2 型糖尿病(T2DM)大鼠脂肪细胞葡萄糖转运以及磷脂酰肌醇激酶-3(PI3K) /蛋白激酶B(Akt)信号通路的影响?方法 将90 只SD 大鼠随机分为正常组?模型组(高脂肪喂养)?姜黄素低剂量组(50 mg/ kg)?姜黄素中剂量组(150 mg/ kg)?姜黄素高剂量组(250 mg/ kg)?罗格列酮组(1. 35 mg/ kg),每组15只?给药后即刻?给药2 周末?给药8 周末测量大鼠体重,给药8 周末禁食12 h 采集血液,分别检测空腹血糖(FBG)?空腹胰岛素(FINS)表达?计算胰岛素抵抗指数(HOMA-IR),甘油三酯(TG)?低/ 高密度脂蛋白胆固醇(LDC-C/ HDL-C)?总胆固醇(TC)表达?正糖钳实验测定葡萄糖灌注速率,荧光免疫实验检测脂肪细胞膜葡萄糖转运蛋白4(GluT4)移位情况,实时荧光定量PCR(qRT-PCR)检测脂肪细胞中GluT4,蛋白质免疫印迹检测脂肪细胞内?外膜中GluT4?p-PI3K?胰岛素受体底物2(Irs2)?p-Akt 表达情况?结果 与正常组相比,模型组给药即刻?给药2 周体重升高,给药8 周体重下降;与模型组相比,给药即刻?给药2 周?给药8 周姜黄素治疗组?罗格列酮组体重均降低( P <0. 05)?与正常组相比,模型组FBG?FINS?HOMA-IR?HDC-L?LDC-L?TC?TG 均升高,葡糖糖注射速率呈剂量依赖性降低;模型组GluT4 mRNA 升高,GluT4?Irs2?p-PI3K/ PI3K?pAkt/ Akt 蛋白表达明显降低;上述差异均有统计学意义( P <0. 05)?与模型组相比,姜黄素治疗组?罗格列酮组FBG?FINS?HOMA-IR?HDC-L?LDC-L?TC?TG 水平均明显降低;葡糖糖注射速率明显升高;GluT4 mRNA 降低,GluT4?Irs2?p-PI3K/ PI3K?pAkt/ Akt 蛋白表达明显升高;上述差异均有统计学意义( P <0. 05),且三组姜黄素剂量组间比较差异也具有统计学意义( P <0. 05)?结论 姜黄素可提高T2DM 型大鼠胰岛素敏感性,可能是激活PI3K/ Akt 信号通路从而促进脂肪细胞GluT4 膜转运,提高脂肪细胞对葡萄糖摄取,进而缓解血糖代谢平衡来实现的?

    Abstract:

    Objective To investigate the effects of curcumin on glucose transport and phosphatidylinositol 3-kinase (PI3K) / protein kinase B (Akt) signaling pathway in adipocytes of type 2 diabetes mellitus (T2DM) rats. MethodsNinety Sprague-Dawley (SD) rats were randomly divided into normal group, model group (high-fat diet-fed), curcuminlow-dose group (50 mg/ kg), curcumin medium-dose group (150 mg/ kg), and curcumin high-dose group (250 mg/ kg)groups, and rosiglitazone group (1. 35 mg/ kg), each group comprised 15 rats. The body weight of rats was measuredimmediately after administration, 2 weeks after administration and 8 weeks after administration, and blood was collected for12 hours after fasting at the end of 8 weeks, fasting blood glucose (FBG), fasting insulin (FINS), the insulin resistanceindex (HOMA-IR), triglyceride (TG), low/ high-density lipoprotein cholesterol (LDC-C/ HDL-C), and total cholesterol(TC) were measured. The glucose perfusion rate was measured by positive glucose clamp assay, the translocation of glucosetransporter 4 (GluT4) in adipocyte membrane was detected by fluorescence immunoassay,GluT4 in adipocytes was detectedby real-time fluorescence quantitative PCR (qRT-PCR), the expression of GluT4, p-PI3K, insulin receptor substrate 2(Irs2) and p-Akt in intracellular and extracellular membranes of adipocytes were detected by Western blotting. Results Compared with the normal group, the weight of the model group increased immediately and 2 weeks after administration,and decreased 8 weeks after administration; compared with the model group, the body weight of curcumin treatment groupand rosiglitazone treatment group decreased immediately, 2 weeks and 8 weeks after administration ( P < 0. 05). Comparedwith the normal group, the FBG, FINS, HOMA-IR, HDC-L, LDC-L, TC and TG in the model group increased, and theglucose injection rate decreased in a dose-dependent manner; GluT4 mRNA increased in the model group, the proteinexpression of GluT4, Irs2, p-PI3K/ PI3K and pAkt/ Akt decreased significantly; and the differences were statisticallysignificant ( P < 0. 05). Compared with the model group, the levels of FBG, FINS, HOMA-IR, HDC-L, LDC-L, TC and TGin the curcumin treatment group and rosiglitazone group were significantly lower, the rate of glucose injection was significantlyhigher, GluT4 mRNA decreased, the protein expression of GluT4, Irs2, p-PI3K/ PI3K and pAkt/ Akt increased significantly,and the differences were statistically significant ( P < 0. 05), and the difference of curcumin dosage among the three groupswas also statistically significant ( P < 0. 05). Conclusions Curcumin can increase the insulin sensitivity of T2DM rats,which may be achieved by activating PI3K/ Akt signaling pathway to promote the GluT4 membrane translocation in adipocytesand increase the uptake of glucose by adipocytes, thereby alleviating the balance of blood sugar metabolism.

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陈洁,刘一然.姜黄素对2 型糖尿病大鼠脂肪细胞葡萄糖转运及PI3K/ Akt 信号通路的影响[J].中国比较医学杂志,2019,29(5):90~97.

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  • 收稿日期:2018-10-23
  • 在线发布日期: 2019-06-05
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