Data from: Expression and function of ATP-dependent potassium channels in zebrafish islet β-cells

ATP-sensitive potassium channels (KATP channels) are critical nutrient sensors in many mammalian tissues. In the pancreas, KATP channels are essential for coupling glucose metabolism to insulin secretion. While orthologous genes for many components of metabolism-secretion coupling in mammals are present in lower vertebrates, their expression, functionality, and ultimate impact on body glucose homeostasis are unclear. In this paper we demonstrate that zebrafish islet β-cells express functional KATP channels of similar subunit composition, structure, and metabolic sensitivity to their mammalian counterparts. We further show that pharmacological activation of native zebrafish KATP using diazoxide, a specific KATP channel opener, is sufficient to disturb glucose tolerance in adult zebrafish. That β-cell KATP channel expression and function are conserved between zebrafish and mammals illustrates the evolutionary conservation of islet metabolic sensing from fish to humans, and lends relevance to the use of zebrafish to model islet glucose sensing and diseases of membrane excitability such as neonatal diabetes.ATP敏感性钾通道（ATP-sensitive potassium channels，KATP通道）是多种哺乳动物组织中关键的营养感应因子。在胰腺中，KATP通道对于将葡萄糖代谢与胰岛素分泌进行耦联至关重要。尽管哺乳动物体内代谢-分泌耦联的诸多组分的同源基因在低等脊椎动物中均有存在，但其表达情况、功能特性以及对机体葡萄糖稳态的最终影响尚不明确。本研究证实，斑马鱼胰岛β细胞表达具有功能活性的KATP通道，其亚基组成、结构以及代谢敏感性与哺乳动物的对应通道高度相似。本研究进一步证实，利用特异性KATP通道开放剂二氮嗪（diazoxide）对天然斑马鱼KATP通道进行药理学激活，足以干扰成年斑马鱼的葡萄糖耐量。斑马鱼与哺乳动物在胰岛β细胞KATP通道的表达与功能上具有保守性，这一发现阐明了从鱼类到人类的胰岛代谢感应机制的进化保守性，同时也证实了利用斑马鱼作为模型来研究胰岛葡萄糖感应以及膜兴奋性疾病（如新生儿糖尿病）的合理性。