Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.
Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups.
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葡萄糖延迟了胰岛素诱导的长期禁食象海豹幼崽脂肪中甲状腺激素介导信号的增加。
DOI：
10.1152/ajpregu.00054.2015
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
Ortiz,RudyM
中科院分区：
文献类型：
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作者：
Martinez,Bridget;Soñanez-Organis,JoséG;Viscarra,JoseA;Jaques,JohnT;MacKenzie,DuncanS;Crocker,DanielE;Ortiz,RudyM
哺乳动物的长期食物剥夺通常会降低葡萄糖、胰岛素和甲状腺激素（TH）浓度，以及组织脱碘酶（DI）的含量和活性，这些共同抑制代谢。然而，在海象幼崽中，长时间禁食不会抑制TH水平；它与脂肪促甲状腺素介导的细胞机制上调和脂肪特异性胰岛素抵抗有关。这个明显的悖论的功能相关性和葡萄糖和胰岛素对胰岛素抵抗组织中促肾上腺素介导的信号的影响还没有很好的定义。为了验证我们的假设，即胰岛素增加了长时间禁食幼鼠体内脂肪的促甲状腺激素信号，我们评估了早期和晚期禁食幼鼠在胰岛素输注后促甲状腺激素相关基因的变化。在禁食后期，胰岛素在注射后60分钟分别使DI1、DI2和thrr β-1 mRNA表达增加566%、44%和267%，并在120分钟内降低。此外，我们对禁食后期的幼鼠进行了葡萄糖刺激，以区分胰岛素和葡萄糖介导的对TH信号的影响。与胰岛素诱导的效应相反，直到120min，葡萄糖输注才增加DI1、DI2和thrr β-1的表达，提示葡萄糖延缓了胰岛素诱导效应的发生。数据还表明，禁食时间增加了脂肪促肾上腺素介导的机制对胰岛素的敏感性，其中一些可能是由葡萄糖升高介导的。这些反应在哺乳动物中似乎是独特的，并且在象海豹中进化，以促进它们适应极端的生理条件。
Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition.