间歇性缺氧条件下 Wistar 大鼠实验性糖尿病发病的分子机制分析

T. V. Ivanenko
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Hypoxic training achieves these benefits by heightening insulin sensitivity and reducing blood glucose levels, which can be particularly advantageous for individuals with diabetes. The aim of the work is to determine changes in the expression of genes associated with the course of diabetes under conditions of exposure to intermittent hypoxia in pancreatic tissue samples of Wistar rats. Materials and methods. Analysis of gene expression was used by the polymerase chain reaction method with reverse transcription in real-time using the RT2 Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany), where the pancreas of experimental animals was studied. Results. According to the results of the PCR study of animals with experimental diabetes and the influence of hypoxic training on its course, the activity of the studied genes can be divided as follows: genes with low expression compared to the control group of animals, where ∆∆Cт <30 (Ace; Cd28; Ctla4; Dusp4 ; Enpp1; Foxp3; G6pc; Gcgr; Glp1r; Gpd1; Gsk3b; Hmox1; Ide; Ikbkb; Il10; Il6; Ins1; Nfkb1; Nkx2-1; Parp1; Pdx1; Pik3cd; Pik3r1; Ppargc1a; Ptpn1; Rab4a; Retn; Slc14a2 ; Snap25; Sod2; Stx4; Stxbp1; Stxbp2; Tnf; Tnfrsf1a; Tnfrsf1b; Ucp2; Vamp2; Vegfa); genes in which no significant changes were detected in the samples in relation to the control group (Acly; Adra1a; Adrb3; Agt; Akt2; Aqp2; Ccl5; Ccr2; Ceacam1; Cebpa; Dpp4; Fbp1; Foxc2; Foxg1; Gcg; Gck; Hnf1b; Hnf4a ; Icam1; Ifng; Igfbp5; Il12b; Il4r; Inppl1; Irs1; Irs2; Mapk14; Mapk8; Neurod1; Nos3; Nrf1; Nsf; Ppara; Pparg; Pygl; Sell; Serpine1; Slc2a4; Snap23; Srebf1; Stxbp4; Tgfb1; Trib3 ; Vamp3; Vapa); there are no genes with high expression compared to the control group. Conclusions. The Nkx2-1 genes, Pik3r1, and Slc14a2 in rats subjected to experimental diabetes displayed notably reduced protein expression activity. Hypoxic training demonstrated an impact on mitigating the expression of the Nkx2-1 protein, which suggests that it might affect the mitochondrial muscle respiratory chain, modulate insulin signaling, and potentially rectify molecular deficiencies associated with diabetic nephropathy. Expression of Dpp4 genes, Gck, Ifng, Mapk8, Nsf and Sell in rats with experimental diabetes and the effect of hypoxic training on it were reduced to the level of control (intact) rats. 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引用次数: 0

摘要

有确凿证据表明,糖尿病患者的缺氧训练是一种在间歇性缺氧条件下进行的专门运动。这种方法有望有效控制和提高糖尿病疗效,因为它有可能显著影响体内的新陈代谢和生理过程。糖尿病缺氧训练的关键要素包括旨在激活新陈代谢途径、增强线粒体功能和调节血糖水平的活动。这种干预措施有可能改善胰岛素抵抗,降低血糖,并全面增强心肺功能。缺氧训练通过提高胰岛素敏感性和降低血糖水平来实现这些益处,这对糖尿病患者尤其有利。这项工作的目的是确定 Wistar 大鼠胰腺组织样本在间歇性缺氧条件下与糖尿病病程相关的基因表达变化。材料和方法使用 RT2 Profiler™ PCR 阵列大鼠糖尿病试剂盒(QIAGEN,德国)实时反转录聚合酶链反应法分析基因表达,对实验动物的胰腺进行研究。结果根据对实验性糖尿病动物的 PCR 研究结果以及缺氧训练对糖尿病病程的影响,所研究基因的活性可分为以下几种:与对照组动物相比表达量较低的基因,其中 ∆∆Cт <30(Ace;Cd28;Ctla4;Dusp4;Enpp1;Foxp3;G6pc;Gcgr;Glp1r;Gpd1;Gsk3b;Hmox1;Ide;Ikbkb;Il10;Il6;Ins1;Nfkb1;Nkx2-1;Parp1;Pdx1;Pik3cd;Pik3r1;Ppargc1a;Ptpn1;Rab4a;Retn;Slc14a2;Snap25;Sod2;Stx4;Stxbp1;Stxbp2;Tnf;Tnfrsf1a;Tnfrsf1b;Ucp2;Vamp2;Vegfa);样本中与对照组相比未检测到显著变化的基因(Acly;Adra1a; Adrb3; Agt; Akt2; Aqp2; Ccl5; Ccr2; Ceacam1; Cebpa; Dpp4; Fbp1; Foxc2; Foxg1; Gcg; Gck; Hnf1b; Hnf4a ; Icam1; Ifng; Igfbp5; Il12b; Il4r; Inppl1; Irs1; Irs2; Mapk14; Mapk8; Neurod1;Nos3;Nrf1;Nsf;Ppara;Pparg;Pygl;Sell;Serpine1;Slc2a4;Snap23;Srebf1;Stxbp4;Tgfb1;Trib3;Vamp3;Vapa);与对照组相比,没有高表达基因。结论实验性糖尿病大鼠的 Nkx2-1 基因、Pik3r1 和 Slc14a2 蛋白表达活性明显降低。缺氧训练对减轻 Nkx2-1 蛋白的表达有影响,这表明它可能会影响线粒体肌肉呼吸链,调节胰岛素信号传导,并有可能纠正与糖尿病肾病相关的分子缺陷。实验性糖尿病大鼠体内 Dpp4 基因、Gck、Ifng、Mapk8、Nsf 和 Sell 的表达以及缺氧训练对其的影响均降低到对照组(完整)大鼠的水平。Dpp4基因、Gck、Ifng、Mapk8、Nsf和Sell表达正常化的结果,可能是缺氧训练对与新陈代谢和内分泌系统有关的激素和信号的分子调节机制、对免疫系统和炎症过程的影响以及胰岛素抵抗的影响。
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Analysis of molecular mechanisms of the development of experimental diabetes in Wistar rats under conditions of intermittent hypoxia
There is strong evidence that hypoxic training, within the context of diabetes, constitutes a specialized form of exercise performed under conditions of intermittent hypoxia. This approach holds promise for effectively managing and enhancing diabetes outcomes, as it has the potential to influence metabolism and physiological processes within the body significantly. The key elements of hypoxic training in diabetes encompass activities geared toward activating metabolic pathways, enhancing mitochondrial function, and regulating blood glucose levels. Such interventions can potentially lead to improvements in insulin resistance, a reduction in glycemia, and an overall enhancement of cardiorespiratory function. Hypoxic training achieves these benefits by heightening insulin sensitivity and reducing blood glucose levels, which can be particularly advantageous for individuals with diabetes. The aim of the work is to determine changes in the expression of genes associated with the course of diabetes under conditions of exposure to intermittent hypoxia in pancreatic tissue samples of Wistar rats. Materials and methods. Analysis of gene expression was used by the polymerase chain reaction method with reverse transcription in real-time using the RT2 Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany), where the pancreas of experimental animals was studied. Results. According to the results of the PCR study of animals with experimental diabetes and the influence of hypoxic training on its course, the activity of the studied genes can be divided as follows: genes with low expression compared to the control group of animals, where ∆∆Cт <30 (Ace; Cd28; Ctla4; Dusp4 ; Enpp1; Foxp3; G6pc; Gcgr; Glp1r; Gpd1; Gsk3b; Hmox1; Ide; Ikbkb; Il10; Il6; Ins1; Nfkb1; Nkx2-1; Parp1; Pdx1; Pik3cd; Pik3r1; Ppargc1a; Ptpn1; Rab4a; Retn; Slc14a2 ; Snap25; Sod2; Stx4; Stxbp1; Stxbp2; Tnf; Tnfrsf1a; Tnfrsf1b; Ucp2; Vamp2; Vegfa); genes in which no significant changes were detected in the samples in relation to the control group (Acly; Adra1a; Adrb3; Agt; Akt2; Aqp2; Ccl5; Ccr2; Ceacam1; Cebpa; Dpp4; Fbp1; Foxc2; Foxg1; Gcg; Gck; Hnf1b; Hnf4a ; Icam1; Ifng; Igfbp5; Il12b; Il4r; Inppl1; Irs1; Irs2; Mapk14; Mapk8; Neurod1; Nos3; Nrf1; Nsf; Ppara; Pparg; Pygl; Sell; Serpine1; Slc2a4; Snap23; Srebf1; Stxbp4; Tgfb1; Trib3 ; Vamp3; Vapa); there are no genes with high expression compared to the control group. Conclusions. The Nkx2-1 genes, Pik3r1, and Slc14a2 in rats subjected to experimental diabetes displayed notably reduced protein expression activity. Hypoxic training demonstrated an impact on mitigating the expression of the Nkx2-1 protein, which suggests that it might affect the mitochondrial muscle respiratory chain, modulate insulin signaling, and potentially rectify molecular deficiencies associated with diabetic nephropathy. Expression of Dpp4 genes, Gck, Ifng, Mapk8, Nsf and Sell in rats with experimental diabetes and the effect of hypoxic training on it were reduced to the level of control (intact) rats. As a result of the normalization of Dpp4 gene expression, Gck, Ifng, Mapk8, Nsf and Sell may be the influence of the effects of hypoxic training on molecular mechanisms of regulation of hormones and signals related to metabolism and the endocrine system, effects on the immune system and inflammatory processes, as well as insulin resistance.
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