Correlation of IDE gene rs11187007 locus polymorphism with insulin resistance and systemic inflammatory response in patients with GDM

Objective:To study the correlation of insulin-degrading enzyme (IDE) gene rs11187007 locus polymorphism with insulin resistance and systemic inflammatory response in patients with gestational diabetes mellitus (GDM).Methods: The pregnant women diagnosed with GDM in our hospital between March 2015 and January 2018 were selected as the GDM group, and healthy pregnant women who had prenatal examination and gave birth during the same period were selected as the control group. Peripheral blood was collected to measure the genotype of IDE gene rs11187007 locus as well as the contents of cytokines IL-6, IL-10, TNF-α, Chemerin and Omentin-1, and placenta was collected to measure the expression levels of IRS-1, IRS-2, GLUT3 and GLUT4.Results: The constituent ratio of IDE gene rs11187007 locus AA genotype, IL-10 and Omentin-1 contents in peripheral blood as well as IRS-1, IRS-2, GLUT3 and GLUT4 mRNA expression levels in placenta of GDM group were all lower than those of control group whereas the constituent ratio of IDE gene rs11187007 locus AG genotype and GG genotype as well as IL-6, TNF-α and Chemerin contents in peripheral blood were higher than those of control group;IRS-1, IRS-2, GLUT3 and GLUT4 mRNA expression levels in the GDM placenta with AG genotype and GG genotype as well as IL-10 and Omentin-1 contents in the peripheral blood were lower than those in the GDM placenta with AA genotype whereas IL-6, TNF-α and Chemerin contents in the peripheral blood were higher than those in the GDM placenta with AA genotype.Conclusion: The mutation from IDE gene rs11187007 allele A to G in GDM patients can aggravate the insulin resistance and systemic inflammatory response.

氯喹对胰岛素抵抗大鼠胰岛素降解酶基因及酶蛋白表达的影响

目的了解氯喹对大鼠肝脏胰岛素降解酶(insulin-degrading enzyme,IDE)基因表达(expression of IDE gene,EIG)及酶蛋白表达(expression of IDE protein,EIP)水平的影响.方法以高脂肪饮食喂养法复制的胰岛素抵抗(insulin resistance,IR)Wistar大鼠模型为对象,检测IR大鼠肝脏EIG,EIP水平和肝脏IDE活性,并测定大鼠的平均葡萄糖输注率(glucose infusion rate,GIR60-120),同时观察氯喹对上述指标的影响.结果IR大鼠的EIG,EIP水平显著高于常规饲料喂养的对照大鼠.服用氯喹后,IR大鼠EIG,EIP水平显著降低,对照大鼠的上述指标无明显改变.IR大鼠和对照大鼠的肝脏IDE活性均与EIG,EIP水平呈显著正相关,而与GIR60-120呈显著负相关.结论氯喹降低IR大鼠IDE活性可能是通过抑制IDE基因转录,从而降低IDE酶蛋白表达量来实现.

慢性束缚应激致大鼠持续性高血糖症与孤束核损伤有关

目的探讨孤束核联合亚核前部(ac NTS)损伤在慢性束缚应激(CRS)所致的胰岛素抵抗性高血糖症发生中的作用。方法采用CRS大鼠模型(n=20;7 d束缚+3 d自由活动,共40 d),检测葡萄糖代谢相关指标。结果 CRS导致约1/3的个体(n=7)持续性的中度胰岛素抵抗性高血糖(空腹血糖不超过11 mmol/L)。CRS高血糖鼠ac NTS可观察到神经元染色浓缩,Caspase-3表达和TUNEL阳性染色,提示出现神经元凋亡样改变。机械损伤ac NTS(n=6),空腹血糖水平逐渐升高,也能导致胰岛素抵抗性高血糖,且高胰岛素血症、胰岛平均体积增大和血清皮质酮水平不变等特点与CRS小鼠一致。结论 CRS损伤了ac NTS的葡萄糖敏感神经元,从而使血糖调节紊乱。

糖尿病大鼠组织的蛋白酪氨酸磷酸酶活性变化

目的:研究蛋白酪氨酸磷酸酶(PTPase)与胰岛素抵抗的关系。方法:链脲佐菌素(STZ)诱发大鼠糖尿病,ELISA法测定糖尿病大鼠各组织器官的PTPase活性,并与正常大鼠进行比较。结果:STZ-糖尿病大鼠肝脏和骨骼肌的PTPase活性升高分别为78%和50%。结论:胰岛素靶细胞的PTPase活性变化与胰岛素抵抗的病因密切相关。

水果酵素醋对胰岛素抵抗糖脂代谢紊乱大鼠的影响

目的探讨水果酵素醋对胰岛素抵抗糖/脂代谢紊乱大鼠的作用。方法SD大鼠随机分为5组:正常组、模型组、水果酵素醋低[玫瑰茄7.95 g(生药)/kg+桃金娘4.82 g(生药)/kg]、中[玫瑰茄15.90 g(生药)/kg+桃金娘9.64 g(生药)/kg]、高剂量[玫瑰茄47.72 g(生药)/kg+桃金娘28.92 g(生药)/kg]组。以高脂饲料喂养联合一次性腹腔注射链脲佐菌素(STZ)复制胰岛素抵抗糖脂代谢紊乱大鼠模型,以糖耐量血糖、血糖曲线下面积(AUC)、血清胰岛素(INS)、胰岛素抵抗指数(IRI)、甘油三酯(TG)、总胆固醇(TC)、尿素氮(BUN)及肌酐(Cr)含量为评价指标,研究水果酵素醋对胰岛素抵抗糖/脂代谢紊乱大鼠的作用。结果与模型组相比,水果酵素醋中、高剂量组0、0.5、2 h糖耐量血糖值及曲线下面积明显降低(P<0.01),尿素氮含量显著下降(P<0.01)。结论水果酵素醋具有辅助降血糖的功能,并具有一定的减轻肾功能损伤作用。