匙羹藤总皂苷干预KK-Ay小鼠胰岛素抵抗及作用机制研究
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摘要
本文由综述部分和实验部分组成,综述部分由2型糖尿病胰岛素抵抗发病机制研究进展、中药活性成分抗糖尿病作用机制研究进展以及匙羹藤现代药理作用研究进展三部分组成。实验部分由匙羹藤总皂苷对KK-Ay小鼠的干预作用、匙羹藤总皂苷对KK-Ay小鼠脂肪组织胰岛素信号通路的影响两部分组成。
实验部分一匙羹藤总皂苷对KK-Ay小鼠的干预作用
目的：观察匙羹藤总皂苷对2型糖尿病KK-Ay小鼠血糖、血脂以及胰岛素抵抗的干预作用。方法：以自发型2型糖尿病胰岛素抵抗小鼠(KK-Ay小鼠)为实验对象,将成模KK-Ay小鼠随机分为模型组、吡格列酮组(每天4.05mg/g体重)、匙羹藤总皂苷组A(每天15g生药材/g体重),选取C57BL/6J小鼠随机分为正常组,匙羹藤总皂苷给药组B(每天15g生药材/g体重),进行以下研究：1、每周观察血糖、体重以及摄食量变化情况；2、第4、8周进行口服葡萄糖耐量(OGTT)实验,计算曲线下面积；3、实验结束后,取血清用生化法测定血总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白浓度,用放免法测定空腹血清胰岛素(Fins)浓度,并计算胰岛素敏感指数(ISI)。结果：①在给药过程中,模型组小鼠在8周实验的过程中空腹血糖呈逐渐上升的趋势。与模型组相比,吡格列酮组小鼠空度血糖在给药5周后开始降低(P<0.05,P<0.01)并持续到实验结束,匙羹藤总皂苷组A在给药4周后开始显著降低(P<0.01),并持续到实验结束；与正常组小鼠相比,模型组血糖显著升高(P<0.01),匙羹藤总皂苷组B小鼠血糖没有变化。②在给药过程中,模型组小鼠体重从实验开始到第6周逐渐增高,从第6周到第8周略有下降趋势。与模型组相比,吡格列酮组小鼠体重从第7周开始降低(P<0.05),匙羹藤总皂苷给药组A从第3周开始降低(P<0.05),从第4周开始显著降低,并持续到实验结束；与正常组小鼠相比,模型组小鼠体重明显升高(P<0.01),匙羹藤总皂苷组B小鼠体重没有变化。③与正常组相比,模型组FPG、Fins水平明显升高(P<0.01),ISI明显降低(P<0.01),匙羹藤总皂苷组BFPG、Fins、ISI没有差异性改变；与模型组相比,吡格列酮组FPG、Fins水平降低(P<0.05,P<0.01),ISI升高(P<0.01),匙羹藤总皂苷组AFPG、Fins水平降低(P<0.05),ISI升高(P<0.05)。④药物干预8周后,与正常组相比,模型组小鼠总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白均明显高于(P<0.01),匙羹藤总皂苷给药组B血脂没有差异性变化；与模型组相比,匙羹藤总皂苷组A甘油三酯、低密度脂蛋白有所降低(P<0.05),总胆固醇,高密度脂蛋白水平没有明显改变。⑤第四周：与正常组相比,模型组曲线下面积(AUC)明显升高(P<0.01),匙羹藤总皂苷组B没有差异性改变；与模型组相比,吡格列酮组AUC降低(P<0.05),匙羹藤总皂苷组AAUC明显降低(P<0.01)。第八周：与正常组相比,模型组AUC明显升高(P<0.01),匙羹藤总皂苷组B没有差异性改变；与模型组相比,吡格列酮组AUC明显降低(P<0.01),匙羹藤总皂苷组A AUC明显降低(P<0.01)。结论：匙羹藤总皂苷对具有胰岛素抵抗特征的2型糖尿病KK-Ay小鼠有治疗作用,并推测与改善胰岛素抵抗有关。
实验部分二匙羹藤总皂苷对KK-Ay小鼠脂肪组织胰岛素信号通路的影响
目的：探讨匙羹藤总皂苷对2型糖尿病KK-Ay小鼠脂肪组织胰岛素信号通路的影响。方法：以27只自发型2型糖尿病胰岛素抵抗小鼠(KK-Ay小鼠)为实验对象,将成模KK-Ay小鼠随机分为模型组、吡格列酮组(每天4.05mg/g体重)、匙羹藤总皂苷组A(每天15g生药材/g体重),选取9只C57BL/6J小鼠随机分为正常组,进行以下研究：1、采用蛋白免疫印迹法测定脂肪组织中蛋白激酶B (AKT), P-AKT (Ser473), P-AKT (Thr308)、PDK-1蛋白表达量；2、采用实时荧光PCR法测定脂肪组织中PPAR γ mRNA、 APNmRNA、PI3κ-p85mRNA、PTENmRNA、GmT4mRNA、CAPmRNA的表达量。结果：①与正常组相比,模型组脂肪组织PPAR γ mRNA表达量降低(P<0.01)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织PPAR γ mRNA均增加(P<0.05)。②与正常组相比,模型组脂肪组织APNmRNA表达量降低(P<0.05)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织APNmRNA表达量均增加(P<0.01)。③与正常组相比,模型组脂肪组织PI3κ-p85mRNA表达量降低(P<0.05)；与模型组相比,匙羹藤总皂苷组A小鼠脂肪组织PI3κ-p85mRNA增加(P<0.05)。④与正常组相比,模型组P-AKT (Thr308)蛋白表达量显著降低(P<0.01)；与模型组相比,吡格列酮组小鼠脂肪组织P-AKT (Thr308)蛋白表达量升高(P<0.05),匙羹藤总皂苷组A小鼠脂肪组织P-AKT (Thr308)蛋白表达量显著升高(P<0.01)。与正常组相比,模型组P-AKT (Ser473)蛋白表达量降低(P<0.05)；与模型组相比,匙羹藤总皂苷组A小鼠脂肪组织P-AKT (Ser473)蛋白表达量升高(P<0.05)。与正常组相比,模型组AKT第308位Thr磷酸化程度显著降低(P<0.01)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠AKT第308位Thr磷酸化程度均显著升高(P<0.01)。与正常组相比,模型组AKT第473位Ser磷酸化程度显著降低(P<0.01)；与模型组相比,匙羹藤总皂苷组A小鼠AKT第473位Ser磷酸化程度显著升高(P<0.01)。⑤与正常组相比,模型组脂肪组织PDK-1蛋白表达量显著增加(P<0.01)；与模型组相比,吡格列酮组小鼠脂肪组织PDK-1蛋白表达量降低(P<0.05),匙羹藤总皂苷组A小鼠脂肪组织PDK1蛋白表达量显著降低(P<0.01)。⑥与正常组相比,模型组脂肪组织PTENmRNA表达量没有显著变化,但是与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织PTENmRNA降低(P<0.05)。⑦与正常组相比,模型组脂肪组织GluT4mRNA表达量降低(P<0.05),与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织GluT4mRNA显著升高(P<0.01)。⑧与正常组相比,模型组脂肪组织CAPmRNA表达量显著降低(P<0.01),与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织CAPmRNA显著升高(P<0.01)。结论：匙羹藤总皂苷可通过作用于脂肪组织胰岛素介导的信号通路缓解胰岛素抵抗。
The present work is composed of two parts:The parts of review and experiment. The review is composed of there parts:The progress of insulin resistance in the pathogenesis of type2diabetes; Progress of Anti-diabetes Mechanism of The active ingredients of Chinese medicine; Research on the modern pharmacological of Gymnema sylvestre. The experiment is composed of two parts:The intervention of Gymnema sylvestre total saponins on KK-Ay mice; Effects of Gymnema sylvestre total saponins on KK-Ay mice in signal transduction pathway
1. The intervention of Gymnema sylvestre total saponins in KK-Ay mice
Objective:To investigate the effects of Gymnema sylvestre total saponins in T2DM mice. Methods:27KK-Ay mice were divided randomly according to body weight level into Model group, group A of Gymnema sylvestre total saponins、Pioglitazone group and18normal C57BL/6J mice as blank group and group B of Gymnema sylvestre total saponins. Fasting plasma glucose (FPG) and the weights of all mice were tested at every weekend, OGTTs were tested at4th,8th weekend and at the end of the experiment all animals were tested FPG, triglyceride (TG), cholesterol total (TC), low densith lipoprotein (LDL-C), high densith lipoprotein (HDL-C), and fasting insulin level (Fins) for evaluating Insulin Sensitivity Index (ISI). Results:①During the admmistration, fasting blood glucose of the mice in model group showed a rising trend in the8-week course of the experiment. Compared with model group, the FPG of KK-Ay mice after administration of pioglitazone began to decrease form the5th weekend{P<0.05, P<0.01) to the end; after administration of Gymnema sylvestre total saponins, the FPGs began to decrease form the4th weekend (P<0.01) to the end. Compared with blank group, the FPG of C57BL/6J mice after administration of Gymnema sylvestre total saponins showed no changing, the FPG of KK-Ay mice in model group showed higher(.P<0.01).②During the administration, the body weights of the mice in model group showed a rising trend in the8-week course of the experiment. Compared with model group, the body weights of KK-Ay mice after administration of pioglitazone began to decrease form the7th weekend (P<0.05) to the end, after administration of pioglitazone began to decrease form the3th weekend (P<0.05, P<0.01) to the end. Compared with blank group, the body weights of C57BL/6J mice after administration of Gymnema sylvestre total saponins showed no changing, the body weights of KK-Ay mice in model group showed higher(P<0.01).③Compared with blank group, model group FPG the Fins level significantly increased (P <0.01), the ISI was significantly lower (P<0.01), FPG, Fins, ISI in group B of Gymnema sylvestre total saponin showed no changing; compared with model group, the pioglitazone group FPG, Fins level decreased (P<0.05, P<0.01), ISI increased(P<0.01), FPG, FinS of the Gymnema sylvestre total saponin group A were decreased (P<0.05) the ISI were elevated (P<0.05).①After8weeks, compared with the blank group,the levels of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein were significantly higher (P<0.01) in model group, showed no changing in group B of Gymnema sylvestre total saponin. Compared with the model group, the levels of triglyceride and LDL-c in Gymnema sylvestre total saponins A were decreased (P<0.05).②Week4:Compared with blank group, model group AUC was significantly higher (P<0.01), Gymnema sylvestre total saponin group B did not change in difference; compared with the model group, the AUC of pioghtazone group (P<0.05) were lower and the AUC in Gymnema sylvestre total saponins group A were significantly; lower (P<0.01). Week8:Compared with blank group, model group AUC was significantly higher (P<0.01), Gymnema sylvestre total saponin group B did not change in difference; compared with the model group, the AUC of pioghtazone group and Gymnema sylvestre total saponins group A were significantly lower (P<0.01). Conclusion:The Gymnema sylvestre total saponins have a therapeutic effect in type2diabetes, and speculated that the effects were related with the improving of insulin resistance.
2. The effects of Gymnema sylvestre total saponin on signal pathway in adipose tissue of KK-Ay mice
Objective:To investigate the molecular mechanism of Gymnema sylvestre total saponin on insulin resistance in adipose tissue of KK-Ay mice Methods:27KK-Ay mice were divided randomly according to body weight level into Model group, group A of Gymnema sylvestre total saponins, Pioghtazone group and9normal C57BL/6J mice as blank group. The expressions of AKT, P-AKT (Ser473), P-AKT (Thr308), PDK-1in adipose tissue were determined using Western blotting. The expressions of AKT, P-AKT (Ser473), P-AKT (Thr308)、PDK-1in adipose tissue were determined using Western blotting. The expressions of PPARγmRNA、APNmRNA、PI3K-p85mRNA、PTENmRNA、GluT4mRNA、CAPmRNA were determined using real-time PCR. Results:①Compared with blank group, the expressions of PPARymRNA in adipose tissue of model group were reduced (P<0.01); compared with model group, the expressions of PPARymRNA in adipose tissue of pioghtazone group and the Gymnema sylvestre the total saponins group A were increased (P <0.05).②Compared with blank group, the expressions of APNmRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of APNmRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P<0.01).③Compared with blank group, the expressions of PI3κ-p85mRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of PI3κ-p85mRNA in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.05).④Compared with blank group, the expressions of P-AKT (Thr308) in adipose tissue of model group were reduced (P<0.01; compared with model group, the expressions of P-AKT (Thr308) in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were increased (P <0.05, P<0.01); Compared with blank group, the expressions of P-AKT(Ser473) in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of P-AKT (Ser473) in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.05); Compared with blank group, the rates of P-AKT (Thr308)/AKT in adipose tissue of model group were reduced (P<0.01); compared with model group, the rates of P-AKT (Thr308)/AKT in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were increased (P<0.01); Compared with blank group, the rates of P-AKT (Ser473)/AKT in adipose tissue of model group were reduced (P<0.01); compared with model group, he rates of P-AKT(Ser473)/AKT in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.01).⑤Compared with blank group, the expressions of PDK-1in adipose tissue of model group were increased (P<0.01); compared with model group, the expressions of PDK-1in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were decreased (P<0.05, P <0.01).⑥Compared with blank group, the expressions of PTENmRNA in adipose tissue of model group showed no changing; compared with model group, the expressions of PTENmRNA in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were decreased (P<0.05).⑦Compared with blank group, the expressions of GluT4mRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of GluT4mRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P<0.01).⑤Compared with blank group, the expressions of CAPmRNA in adipose tissue of model group were reduced (P <0.01); compared with model group, the expressions of CAPmRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P <0.01).Conclusion:Gymnema sylvestre total saponins improved insulin resistance via acting on the signal pathway mediated by insulin in adipose.
实验部分一匙羹藤总皂苷对KK-Ay小鼠的干预作用
目的：观察匙羹藤总皂苷对2型糖尿病KK-Ay小鼠血糖、血脂以及胰岛素抵抗的干预作用。方法：以自发型2型糖尿病胰岛素抵抗小鼠(KK-Ay小鼠)为实验对象,将成模KK-Ay小鼠随机分为模型组、吡格列酮组(每天4.05mg/g体重)、匙羹藤总皂苷组A(每天15g生药材/g体重),选取C57BL/6J小鼠随机分为正常组,匙羹藤总皂苷给药组B(每天15g生药材/g体重),进行以下研究：1、每周观察血糖、体重以及摄食量变化情况；2、第4、8周进行口服葡萄糖耐量(OGTT)实验,计算曲线下面积；3、实验结束后,取血清用生化法测定血总胆固醇、甘油三酯、低密度脂蛋白、高密度脂蛋白浓度,用放免法测定空腹血清胰岛素(Fins)浓度,并计算胰岛素敏感指数(ISI)。结果：①在给药过程中,模型组小鼠在8周实验的过程中空腹血糖呈逐渐上升的趋势。与模型组相比,吡格列酮组小鼠空度血糖在给药5周后开始降低(P<0.05,P<0.01)并持续到实验结束,匙羹藤总皂苷组A在给药4周后开始显著降低(P<0.01),并持续到实验结束；与正常组小鼠相比,模型组血糖显著升高(P<0.01),匙羹藤总皂苷组B小鼠血糖没有变化。②在给药过程中,模型组小鼠体重从实验开始到第6周逐渐增高,从第6周到第8周略有下降趋势。与模型组相比,吡格列酮组小鼠体重从第7周开始降低(P<0.05),匙羹藤总皂苷给药组A从第3周开始降低(P<0.05),从第4周开始显著降低,并持续到实验结束；与正常组小鼠相比,模型组小鼠体重明显升高(P<0.01),匙羹藤总皂苷组B小鼠体重没有变化。③与正常组相比,模型组FPG、Fins水平明显升高(P<0.01),ISI明显降低(P<0.01),匙羹藤总皂苷组BFPG、Fins、ISI没有差异性改变；与模型组相比,吡格列酮组FPG、Fins水平降低(P<0.05,P<0.01),ISI升高(P<0.01),匙羹藤总皂苷组AFPG、Fins水平降低(P<0.05),ISI升高(P<0.05)。④药物干预8周后,与正常组相比,模型组小鼠总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白均明显高于(P<0.01),匙羹藤总皂苷给药组B血脂没有差异性变化；与模型组相比,匙羹藤总皂苷组A甘油三酯、低密度脂蛋白有所降低(P<0.05),总胆固醇,高密度脂蛋白水平没有明显改变。⑤第四周：与正常组相比,模型组曲线下面积(AUC)明显升高(P<0.01),匙羹藤总皂苷组B没有差异性改变；与模型组相比,吡格列酮组AUC降低(P<0.05),匙羹藤总皂苷组AAUC明显降低(P<0.01)。第八周：与正常组相比,模型组AUC明显升高(P<0.01),匙羹藤总皂苷组B没有差异性改变；与模型组相比,吡格列酮组AUC明显降低(P<0.01),匙羹藤总皂苷组A AUC明显降低(P<0.01)。结论：匙羹藤总皂苷对具有胰岛素抵抗特征的2型糖尿病KK-Ay小鼠有治疗作用,并推测与改善胰岛素抵抗有关。
实验部分二匙羹藤总皂苷对KK-Ay小鼠脂肪组织胰岛素信号通路的影响
目的：探讨匙羹藤总皂苷对2型糖尿病KK-Ay小鼠脂肪组织胰岛素信号通路的影响。方法：以27只自发型2型糖尿病胰岛素抵抗小鼠(KK-Ay小鼠)为实验对象,将成模KK-Ay小鼠随机分为模型组、吡格列酮组(每天4.05mg/g体重)、匙羹藤总皂苷组A(每天15g生药材/g体重),选取9只C57BL/6J小鼠随机分为正常组,进行以下研究：1、采用蛋白免疫印迹法测定脂肪组织中蛋白激酶B (AKT), P-AKT (Ser473), P-AKT (Thr308)、PDK-1蛋白表达量；2、采用实时荧光PCR法测定脂肪组织中PPAR γ mRNA、 APNmRNA、PI3κ-p85mRNA、PTENmRNA、GmT4mRNA、CAPmRNA的表达量。结果：①与正常组相比,模型组脂肪组织PPAR γ mRNA表达量降低(P<0.01)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织PPAR γ mRNA均增加(P<0.05)。②与正常组相比,模型组脂肪组织APNmRNA表达量降低(P<0.05)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织APNmRNA表达量均增加(P<0.01)。③与正常组相比,模型组脂肪组织PI3κ-p85mRNA表达量降低(P<0.05)；与模型组相比,匙羹藤总皂苷组A小鼠脂肪组织PI3κ-p85mRNA增加(P<0.05)。④与正常组相比,模型组P-AKT (Thr308)蛋白表达量显著降低(P<0.01)；与模型组相比,吡格列酮组小鼠脂肪组织P-AKT (Thr308)蛋白表达量升高(P<0.05),匙羹藤总皂苷组A小鼠脂肪组织P-AKT (Thr308)蛋白表达量显著升高(P<0.01)。与正常组相比,模型组P-AKT (Ser473)蛋白表达量降低(P<0.05)；与模型组相比,匙羹藤总皂苷组A小鼠脂肪组织P-AKT (Ser473)蛋白表达量升高(P<0.05)。与正常组相比,模型组AKT第308位Thr磷酸化程度显著降低(P<0.01)；与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠AKT第308位Thr磷酸化程度均显著升高(P<0.01)。与正常组相比,模型组AKT第473位Ser磷酸化程度显著降低(P<0.01)；与模型组相比,匙羹藤总皂苷组A小鼠AKT第473位Ser磷酸化程度显著升高(P<0.01)。⑤与正常组相比,模型组脂肪组织PDK-1蛋白表达量显著增加(P<0.01)；与模型组相比,吡格列酮组小鼠脂肪组织PDK-1蛋白表达量降低(P<0.05),匙羹藤总皂苷组A小鼠脂肪组织PDK1蛋白表达量显著降低(P<0.01)。⑥与正常组相比,模型组脂肪组织PTENmRNA表达量没有显著变化,但是与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织PTENmRNA降低(P<0.05)。⑦与正常组相比,模型组脂肪组织GluT4mRNA表达量降低(P<0.05),与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织GluT4mRNA显著升高(P<0.01)。⑧与正常组相比,模型组脂肪组织CAPmRNA表达量显著降低(P<0.01),与模型组相比,吡格列酮组、匙羹藤总皂苷组A小鼠脂肪组织CAPmRNA显著升高(P<0.01)。结论：匙羹藤总皂苷可通过作用于脂肪组织胰岛素介导的信号通路缓解胰岛素抵抗。
The present work is composed of two parts:The parts of review and experiment. The review is composed of there parts:The progress of insulin resistance in the pathogenesis of type2diabetes; Progress of Anti-diabetes Mechanism of The active ingredients of Chinese medicine; Research on the modern pharmacological of Gymnema sylvestre. The experiment is composed of two parts:The intervention of Gymnema sylvestre total saponins on KK-Ay mice; Effects of Gymnema sylvestre total saponins on KK-Ay mice in signal transduction pathway
1. The intervention of Gymnema sylvestre total saponins in KK-Ay mice
Objective:To investigate the effects of Gymnema sylvestre total saponins in T2DM mice. Methods:27KK-Ay mice were divided randomly according to body weight level into Model group, group A of Gymnema sylvestre total saponins、Pioglitazone group and18normal C57BL/6J mice as blank group and group B of Gymnema sylvestre total saponins. Fasting plasma glucose (FPG) and the weights of all mice were tested at every weekend, OGTTs were tested at4th,8th weekend and at the end of the experiment all animals were tested FPG, triglyceride (TG), cholesterol total (TC), low densith lipoprotein (LDL-C), high densith lipoprotein (HDL-C), and fasting insulin level (Fins) for evaluating Insulin Sensitivity Index (ISI). Results:①During the admmistration, fasting blood glucose of the mice in model group showed a rising trend in the8-week course of the experiment. Compared with model group, the FPG of KK-Ay mice after administration of pioglitazone began to decrease form the5th weekend{P<0.05, P<0.01) to the end; after administration of Gymnema sylvestre total saponins, the FPGs began to decrease form the4th weekend (P<0.01) to the end. Compared with blank group, the FPG of C57BL/6J mice after administration of Gymnema sylvestre total saponins showed no changing, the FPG of KK-Ay mice in model group showed higher(.P<0.01).②During the administration, the body weights of the mice in model group showed a rising trend in the8-week course of the experiment. Compared with model group, the body weights of KK-Ay mice after administration of pioglitazone began to decrease form the7th weekend (P<0.05) to the end, after administration of pioglitazone began to decrease form the3th weekend (P<0.05, P<0.01) to the end. Compared with blank group, the body weights of C57BL/6J mice after administration of Gymnema sylvestre total saponins showed no changing, the body weights of KK-Ay mice in model group showed higher(P<0.01).③Compared with blank group, model group FPG the Fins level significantly increased (P <0.01), the ISI was significantly lower (P<0.01), FPG, Fins, ISI in group B of Gymnema sylvestre total saponin showed no changing; compared with model group, the pioglitazone group FPG, Fins level decreased (P<0.05, P<0.01), ISI increased(P<0.01), FPG, FinS of the Gymnema sylvestre total saponin group A were decreased (P<0.05) the ISI were elevated (P<0.05).①After8weeks, compared with the blank group,the levels of total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein were significantly higher (P<0.01) in model group, showed no changing in group B of Gymnema sylvestre total saponin. Compared with the model group, the levels of triglyceride and LDL-c in Gymnema sylvestre total saponins A were decreased (P<0.05).②Week4:Compared with blank group, model group AUC was significantly higher (P<0.01), Gymnema sylvestre total saponin group B did not change in difference; compared with the model group, the AUC of pioghtazone group (P<0.05) were lower and the AUC in Gymnema sylvestre total saponins group A were significantly; lower (P<0.01). Week8:Compared with blank group, model group AUC was significantly higher (P<0.01), Gymnema sylvestre total saponin group B did not change in difference; compared with the model group, the AUC of pioghtazone group and Gymnema sylvestre total saponins group A were significantly lower (P<0.01). Conclusion:The Gymnema sylvestre total saponins have a therapeutic effect in type2diabetes, and speculated that the effects were related with the improving of insulin resistance.
2. The effects of Gymnema sylvestre total saponin on signal pathway in adipose tissue of KK-Ay mice
Objective:To investigate the molecular mechanism of Gymnema sylvestre total saponin on insulin resistance in adipose tissue of KK-Ay mice Methods:27KK-Ay mice were divided randomly according to body weight level into Model group, group A of Gymnema sylvestre total saponins, Pioghtazone group and9normal C57BL/6J mice as blank group. The expressions of AKT, P-AKT (Ser473), P-AKT (Thr308), PDK-1in adipose tissue were determined using Western blotting. The expressions of AKT, P-AKT (Ser473), P-AKT (Thr308)、PDK-1in adipose tissue were determined using Western blotting. The expressions of PPARγmRNA、APNmRNA、PI3K-p85mRNA、PTENmRNA、GluT4mRNA、CAPmRNA were determined using real-time PCR. Results:①Compared with blank group, the expressions of PPARymRNA in adipose tissue of model group were reduced (P<0.01); compared with model group, the expressions of PPARymRNA in adipose tissue of pioghtazone group and the Gymnema sylvestre the total saponins group A were increased (P <0.05).②Compared with blank group, the expressions of APNmRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of APNmRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P<0.01).③Compared with blank group, the expressions of PI3κ-p85mRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of PI3κ-p85mRNA in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.05).④Compared with blank group, the expressions of P-AKT (Thr308) in adipose tissue of model group were reduced (P<0.01; compared with model group, the expressions of P-AKT (Thr308) in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were increased (P <0.05, P<0.01); Compared with blank group, the expressions of P-AKT(Ser473) in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of P-AKT (Ser473) in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.05); Compared with blank group, the rates of P-AKT (Thr308)/AKT in adipose tissue of model group were reduced (P<0.01); compared with model group, the rates of P-AKT (Thr308)/AKT in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were increased (P<0.01); Compared with blank group, the rates of P-AKT (Ser473)/AKT in adipose tissue of model group were reduced (P<0.01); compared with model group, he rates of P-AKT(Ser473)/AKT in adipose tissue of Gymnema sylvestre the total saponins group A were increased (P<0.01).⑤Compared with blank group, the expressions of PDK-1in adipose tissue of model group were increased (P<0.01); compared with model group, the expressions of PDK-1in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were decreased (P<0.05, P <0.01).⑥Compared with blank group, the expressions of PTENmRNA in adipose tissue of model group showed no changing; compared with model group, the expressions of PTENmRNA in adipose tissue of pioglitazone group and Gymnema sylvestre the total saponins group A were decreased (P<0.05).⑦Compared with blank group, the expressions of GluT4mRNA in adipose tissue of model group were reduced (P<0.05); compared with model group, the expressions of GluT4mRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P<0.01).⑤Compared with blank group, the expressions of CAPmRNA in adipose tissue of model group were reduced (P <0.01); compared with model group, the expressions of CAPmRNA in adipose tissue of pioglitazone group and the Gymnema sylvestre the total saponins group A were increased (P <0.01).Conclusion:Gymnema sylvestre total saponins improved insulin resistance via acting on the signal pathway mediated by insulin in adipose.
引文
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