Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation.
Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation.
复制标题
DOI：
10.1016/j.bbadis.2011.02.007
复制
发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Lacombe VA
中科院分区：
文献类型：
--
作者：
Waller AP;Kohler K;Burns TA;Mudge MC;Belknap JK;Lacombe VA
尽管脂肪组织（AT）葡萄糖转运在调节全身胰岛素敏感性中的重要性日益明显，并且胰岛素抵抗（IR）已得到广泛认识，但IR的潜在机制仍不清楚。本研究的目的是通过表征自然发生的代偿性IR的大型动物模型中多个内脏和皮下脂肪库中葡萄糖转运蛋白（GLUT）的变化来确定葡萄糖转运的早期病理变化。 AT 活检是从马身上采集的，根据胰岛素改良频繁采样静脉葡萄糖耐量试验的结果，将马分为胰岛素敏感型 (IS) 或补偿型 IR。通过蛋白质印迹法在多个 AT 库以及 AS160（GLUT 运输途径中的潜在关键参与者）中测量 GLUT4（主要亚型）和 GLUT12（最近发现的亚型之一）的蛋白质表达。使用生物素化双甘露糖光标记技术，对活性细胞表面的过量含量进行定量。在 IS 状态期间，与其他站点相比，网膜 AT 的总过剩含量最高。 IR与网膜AT中总GLUT4含量显着降低相关，而其他内脏或皮下脂肪位点的含量没有变化。此外，与 IS 马相比，IR 的 AT 中活性细胞表面 GLUT-4（而非 -12）显着降低，组间 AS160 磷酸化没有变化。我们的数据表明，尽管 AS160 激活正常，但 GLUT4（而非 GLUT12）是自然发生的补偿性 IR 期间 AT 的致病因素。
Although the importance of adipose tissue (AT) glucose transport in regulating whole-body insulin sensitivity is becoming increasingly evident and insulin resistance (IR) has been widely recognized, the underlying mechanisms of IR are still not well understood. The purpose of the present study was to determine the early pathological changes in glucose transport by characterizing the alterations in glucose transporters (GLUT) in multiple visceral and subcutaneous adipose depots in a large animal model of naturally-occurring compensated IR. AT biopsies were collected from horses, which were classified as insulin-sensitive (IS) or compensated IR based on the results of an insulin-modified frequently-sampled intravenous glucose tolerance test. Protein expression of GLUT4 (major isoform) and GLUT12 (one of the most recently discovered isoforms) were measured by Western blotting in multiple AT depots, as well as AS160 (a potential key player in GLUT trafficking pathway). Using a biotinylated bis-mannose photolabeled technique, active cell surface GLUT content was quantified. Omental AT had the highest total GLUT content compared to other sites during the IS state. IR was associated with a significantly reduced total GLUT4 content in omental AT, without a change in content in other visceral or subcutaneous adipose sites. In addition, active cell surface GLUT-4, but not -12, was significantly lower in AT of IR compared to IS horses, without change in AS160 phosphorylation between groups. Our data suggest that GLUT4, but not GLUT12, is a pathogenic factor in AT during naturally-occurring compensated IR, despite normal AS160 activation.
登录
查看更多内容
影响因子：
7.7
作者：
Karlsson, HKR;Zierath, JR;Wallberg-Henriksson, H
通讯作者：
Wallberg-Henriksson, H
影响因子：
8.2
作者：
Carvalho, E;Eliasson, B;Smith, U
通讯作者：
Smith, U
影响因子：
7.7
作者：
Bergman, RN;Ader, M;Van Citters, G
通讯作者：
Van Citters, G
影响因子：
7.7
作者：
Funai K;Cartee GD
通讯作者：
Cartee GD
影响因子：
4.1
作者：
Koumanov, F;Yang, J;Holman, GD
通讯作者：
Holman, GD