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Loss of endothelin type B receptor function improves insulin sensitivity in rats.

内皮素 B 型受体功能丧失改善大鼠胰岛素敏感性。

  • 影响因子:2.06
  • DOI:10.1139/cjpp-2019-0666
  • 作者列表:"Rivera-Gonzalez OJ","Kasztan M","Johnston JG","Hyndman KA","Speed JS
  • 发表时间:2020-02-21
Abstract

:High salt intake (HS) is associated with obesity and insulin resistance. ET-1, a peptide released in response to HS, inhibits the actions of insulin on cultured adipocytes through ET-1 type B (ETB) receptors; however, the in vivo implications of ETB receptor activation on lipid metabolism and insulin resistance is unknown. We hypothesized that activation of ETB receptors in response to HS intake promotes dyslipidemia and insulin resistance. In normal salt (NS) fed rats, no significant difference in body weight or epidydimal fat mass was observed between control and ETB deficient rats. After 2 weeks of HS, ETB def rats had significantly lower body weight and epidydimal fat mass compared to controls. Non-fasting plasma glucose was not different between genotypes, however plasma insulin concentration was significantly lower in ETB deficient rats compared to controls suggesting improved insulin sensitivity. In addition, ETB deficient rats had higher circulating free fatty acids in both NS and HS groups, with no difference in plasma triglycerides between genotypes. In a separate experiment, ETB deficient rats had significantly lower fasting blood glucose and improved glucose and insulin tolerance compared to controls. These data suggest that ET-1 promotes adipose deposition and insulin resistance via the ETB receptor.

摘要

: 高盐摄入 (HS) 与肥胖和胰岛素抵抗有关。ET-1,一种响应于 HS 释放的肽,通过 B 型 (ETB) 受体抑制胰岛素对培养脂肪细胞 ET-1 作用; 然而, ETB 受体激活对脂质代谢和胰岛素抵抗的体内影响尚不清楚。我们假设对 HS 摄入的反应中 ETB 受体的激活促进了血脂异常和胰岛素抵抗。在正常盐 (NS) 喂养的大鼠中,未观察到对照组和 ETB 缺乏大鼠之间的体重或表皮脂肪量存在显著差异。HS 2 周后,与对照组相比,ETB def 大鼠的体重和脂肪量显著降低。非空腹血糖在基因型之间无差异,但与对照组相比,ETB 缺陷大鼠血浆胰岛素浓度显著降低,提示胰岛素敏感性改善。此外,ETB 缺陷大鼠在 NS 和 HS 组中均有较高的循环游离脂肪酸,基因型间血浆甘油三酯无差异。在另一项实验中,与对照组相比,ETB 缺陷大鼠的空腹血糖显著降低,葡萄糖和胰岛素耐受性改善。这些数据表明,ET-1 通过 ETB 受体促进脂肪沉积和胰岛素抵抗。

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影响因子:2.86
发表时间:2020-01-08
来源期刊:Acta Diabetologica
DOI:10.1007/s00592-019-01469-5
作者列表:["Benhalima, Katrien","Crombrugge, Paul","Moyson, Carolien","Verhaeghe, Johan","Vandeginste, Sofie","Verlaenen, Hilde","Vercammen, Chris","Maes, Toon","Dufraimont, Els","Block, Christophe","Jacquemyn, Yves","Mekahli, Farah","Clippel, Katrien","Den Bruel, Annick","Loccufier, Anne","Laenen, Annouschka","Minschart, Caro","Devlieger, Roland","Mathieu, Chantal"]

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关键词: 暂无
翻译标题与摘要 下载文献
影响因子:19.14
发表时间:2020-01-01
来源期刊:Nature Medicine
DOI:10.1038/s41591-019-0724-8
作者列表:["Artzi, Nitzan Shalom","Shilo, Smadar","Hadar, Eran","Rossman, Hagai","Barbash-Hazan, Shiri","Ben-Haroush, Avi","Balicer, Ran D.","Feldman, Becca","Wiznitzer, Arnon","Segal, Eran"]

METHODS:Leveraging the availability of nationwide electronic health records from over 500,000 pregnancies in Israel, a machine-learning approach offers an alternative means of predicting gestational diabetes at high accuracy in the early stages of pregnancy. Gestational diabetes mellitus (GDM) poses increased risk of short- and long-term complications for mother and offspring^ 1 – 4 . GDM is typically diagnosed at 24–28 weeks of gestation, but earlier detection is desirable as this may prevent or considerably reduce the risk of adverse pregnancy outcomes^ 5 , 6 . Here we used a machine-learning approach to predict GDM on retrospective data of 588,622 pregnancies in Israel for which comprehensive electronic health records were available. Our models predict GDM with high accuracy even at pregnancy initiation (area under the receiver operating curve (auROC) = 0.85), substantially outperforming a baseline risk score (auROC = 0.68). We validated our results on both a future validation set and a geographical validation set from the most populated city in Israel, Jerusalem, thereby emulating real-world performance. Interrogating our model, we uncovered previously unreported risk factors, including results of previous pregnancy glucose challenge tests. Finally, we devised a simpler model based on just nine questions that a patient could answer, with only a modest reduction in accuracy (auROC = 0.80). Overall, our models may allow early-stage intervention in high-risk women, as well as a cost-effective screening approach that could avoid the need for glucose tolerance tests by identifying low-risk women. Future prospective studies and studies on additional populations are needed to assess the real-world clinical utility of the model.

关键词: 暂无
翻译标题与摘要 下载文献
影响因子:4.34
发表时间:2020-01-27
DOI:10.1128/AAC.01777-19
作者列表:["Lowes DJ","Hevener KE","Peters BM"]

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