Matsuda Hiroki, Mullapudi Sri Teja, Zhang Yuxi, Hesselson Daniel, Stainier Didier Y R
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany
Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Diabetes. 2017 Oct;66(10):2623-2635. doi: 10.2337/db16-1476. Epub 2017 Jul 11.
Thyroid hormone (TH) signaling promotes tissue maturation and adult organ formation. Developmental transitions alter an organism's metabolic requirements, and it remains unclear how development and metabolic demands are coordinated. We used the zebrafish as a model to test whether and how TH signaling affects pancreatic islet maturation, and consequently glucose homeostasis, during the larval to juvenile transition. We found that exogenous TH precociously activates the β-cell differentiation genes and while downregulating a master regulator of α-cell development and function. Together, these effects induced hypoglycemia, at least in part by increasing and decreasing expression. We visualized TH target tissues using a novel TH-responsive reporter line and found that both α- and β-cells become targets of endogenous TH signaling during the larval-to-juvenile transition. Importantly, endogenous TH is required during this transition for the functional maturation of α- and β-cells in order to maintain glucose homeostasis. Thus, our study sheds new light on the regulation of glucose metabolism during major developmental transitions.
甲状腺激素（TH）信号传导促进组织成熟和成年器官形成。发育转变会改变生物体的代谢需求，而发育与代谢需求如何协调仍不清楚。我们以斑马鱼为模型，来测试在幼体到幼鱼的转变过程中，TH信号传导是否以及如何影响胰岛成熟，进而影响葡萄糖稳态。我们发现，外源性TH会过早激活β细胞分化基因 和 ，同时下调α细胞发育和功能的主要调节因子 。这些效应共同导致低血糖，至少部分是通过增加 和减少 表达来实现的。我们使用一种新型的TH反应报告系对TH靶组织进行可视化，发现α细胞和β细胞在幼体到幼鱼的转变过程中都成为内源性TH信号的靶标。重要的是，在此转变过程中，内源性TH是α细胞和β细胞功能成熟以维持葡萄糖稳态所必需的。因此，我们的研究为主要发育转变过程中的葡萄糖代谢调节提供了新的见解。
