Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups.
Glut4 is upregulated despite decreased insulin signaling during prolonged fasting in northern elephant seal pups.
复制标题
尽管北象海豹幼崽在长时间禁食期间胰岛素信号减弱，但 Glut4 仍上调。
DOI：
10.1152/ajpregu.00478.2010
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Ortiz,RudyM
中科院分区：
文献类型：
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作者：
Viscarra,JoseA;Vázquez-Medina,JoséPablo;Crocker,DanielE;Ortiz,RudyM
餐后细胞葡萄糖摄取依赖于肌肉和脂肪组织中的胰岛素信号级联，导致胰岛素依赖性葡萄糖转运蛋白4（Glut 4）易位至质膜。此外，延长的食物剥夺的特征在于抑制胰岛素信号传导和降低Glut 4表达。北方象海豹适应长时间的禁食，其特点是血浆葡萄糖水平高。为了解决这一假设，即禁食诱导的胰岛素减少与长期禁食海豹中胰岛素信号转导减少有关，我们比较了早期（n= 9;断奶后2-3周）和晚期（n= 8;断奶后6-8周）禁食海豹之间细胞胰岛素信号转导途径的脂肪蛋白水平、Glut 4和血糖、胰岛素、皮质醇和脂联素浓度。空腹时血浆脂联素（230 ± 13 vs. 177 ± 11 ng/ml）、胰岛素（2.7 ± 0.4 vs. 1.0 ± 0.1 μU/ml）和葡萄糖（9.8 ± 0.5 vs. 8.0 ± 0.3 mM）降低，而皮质醇（124 ± 6 vs. 257 ± 30 nM）加倍。Glut 4增加（31%）与禁食，尽管磷脂酰肌醇3-激酶以及磷酸化胰岛素受体，胰岛素受体底物-1，Akt 2的细胞含量显着下降。增加的Glut 4可能有助于降低血糖，但胰岛素和胰岛素信号的减少表明，在长时间禁食的象海豹中，Glut 4在脂肪组织中不依赖胰岛素。这种不依赖于胰岛素的血糖降低可能使这些动物成为研究胰岛素抵抗的理想模型。
Postprandial cellular glucose uptake is dependent on an insulin-signaling cascade in muscle and adipose tissue, resulting in the translocation of the insulin-dependent glucose transporter 4 (Glut4) into the plasma membrane. Additionally, extended food deprivation is characterized by suppressed insulin signaling and decreased Glut4 expression. Northern elephant seals are adapted to prolonged fasts characterized by high levels of plasma glucose. To address the hypothesis that the fasting-induced decrease in insulin is associated with reduced insulin signaling in prolonged fasted seals, we compared the adipose protein levels of the cellular insulin-signaling pathway, Glut4 and plasma glucose, insulin, cortisol, and adiponectin concentrations between Early (n= 9; 2–3 wks postweaning) and Late (n= 8; 6–8 wks postweaning) fasted seals. Plasma adiponectin (230 ± 13 vs. 177 ± 11 ng/ml), insulin (2.7 ± 0.4 vs. 1.0 ± 0.1 μU/ml), and glucose (9.8 ± 0.5 vs. 8.0 ± 0.3 mM) decreased, while cortisol (124 ± 6 vs. 257 ± 30 nM) doubled with fasting. Glut4 increased (31%) with fasting despite the significant decreases in the cellular content of phosphatidylinositol 3-kinase as well as phosphorylated insulin receptor, insulin receptor substrate-1, and Akt2. Increased Glut4 may have contributed to the decrease in plasma glucose, but the decrease in insulin and insulin signaling suggests that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting in elephant seals. The reduction of plasma glucose independent of insulin may make these animals an ideal model for the study of insulin resistance.