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Insulin resistance in cavefish as an adaptation to a nutrient - limited environment

机译：石斑鱼的胰岛素抵抗适应营养有限的环境

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摘要

Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods(1). Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia. Hybrid fish from surface-cave crosses carrying this mutation weigh more than non-carriers, and zebrafish genetically engineered to carry the mutation have increased body weight and insulin resistance. Higher body weight may be advantageous in caves as a strategy to cope with an infrequent food supply. In humans, the identical mutation in the insulin receptor leads to a severe form of insulin resistance and reduced lifespan. However, cavefish have a similar lifespan to surface fish and do not accumulate the advanced glycation end-products in the blood that are typically associated with the progression of diabetes-associated pathologies. Our findings suggest that diminished insulin signalling is beneficial in a nutrient-limited environment and that cavefish may have acquired compensatory mechanisms that enable them to circumvent the typical negative effects associated with failure to regulate blood glucose levels.
机译：周期性的食物短缺是自然栖息地中生物所面临的主要挑战。穴居动物必须承受长期的营养剥夺，因为在缺乏光合作用的情况下，洞穴取决于外部能源，例如季节性洪水（1）。在这里，我们显示，与河流适应人群相比，适应墨西哥洞穴的墨西哥四胞胎（Astyanax mexicanus）的血糖稳态失调并且对胰岛素具有抵抗力。我们发现，多个洞穴群体在胰岛素受体中携带一个突变，导致体外胰岛素结合减少，并导致高血糖症。携带这种突变的表面凹洞杂交的杂鱼比非携带者的体重重，而经过基因工程改造以携带该突变的斑马鱼则增加了体重和胰岛素抵抗。较高的体重在山洞中可能是有利的，因为这种策略可以应付很少的食物供应。在人类中，胰岛素受体的相同突变会导致严重形式的胰岛素抵抗并缩短寿命。然而，洞穴鱼的寿命与表面鱼类相似，并且不会在血液中积聚高级的糖基化终产物，而这些终末糖化终产物通常与糖尿病相关疾病的进展有关。我们的研究结果表明，在营养有限的环境中，减少胰岛素信号传导是有益的，并且穴鱼可能已获得补偿机制，使它们能够规避与无法调节血糖水平相关的典型负面影响。

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  • 来源
    《Nature》 |2018年第7698期|647-651|共5页
  • 作者

    Riddle Misty R.; Aspiras Ariel C.; Gaudenz Karin; Peuss Robert; Sung Jenny Y.; Martineau Brian; Peavey Megan; Box Andrew C.; Tabin Julius A.; McGaugh Suzanne; Borowsky Richard; Tabin Clifford J.; Rohner Nicolas;

  • 作者单位

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Univ Minnesota, Coll Biomed Sci, St Paul, MN 55108 USA;

    NYU, Dept Biol, New York, NY 10003 USA;

    Harvard Med Sch, Dept Genet, Boston, MA 02115 USA;

    Stowers Inst Med Res, Kansas City, MO 64110 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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