College of Fisheries, Henan Normal University, Xinxiang, 453007, People's Republic of China.
College of Fisheries, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Xinxiang, 453007, People's Republic of China.
BMC Genomics. 2018 Apr 11;19(1):246. doi: 10.1186/s12864-018-4647-4.
Glucose plays a key role as an energy source in most mammals, but its importance in fish appears to be limited that so far seemed to belong to diabetic humans only. Several laboratories worldwide have made important efforts in order to better understand this strange phenotype observed in fish. However, the mechanism of carbohydrate/glucose metabolism is astonishingly complex. Why basal glycaemia is different between fish and mammals and how carbohydrate metabolism is different amongst organisms is largely uncharted territory. The utilization of comparative systems biology with model vertebrates to explore fish metabolism has become an essential approach to unravelling hidden in vivo mechanisms.
In this study, we first built a database containing 791, 593, 523, 666 and 698 carbohydrate/glucose metabolic genes from the genomes of Danio rerio, Xenopus tropicalis, Gallus gallus, Mus musculus and Homo sapiens, respectively, and most of these genes in our database are predicted to encode specific enzymes that play roles in defined reactions; over 57% of these genes are related to human type 2 diabetes. Then, we systematically compared these genes and found that more than 70% of the carbohydrate/glucose metabolic genes are conserved in the five species. Interestingly, there are 4 zebrafish-specific genes (si:ch211-167b20.8, CABZ01043017.1, socs9 and eif4e1c) and 1 human-specific gene (CALML6) that may alter glucose utilization in their corresponding species. Interestingly, these 5 genes are all carbohydrate regulation factors, but the enzymes themselves are involved in insulin regulation pathways. Lastly, in order to facilitate the use of our data sets, we constructed a glucose metabolism database platform ( http://101.200.43.1:10000/ ).
This study provides the first systematic genomic insights into carbohydrate/glucose metabolism. After exhaustive analysis, we found that most metabolic genes are conserved in vertebrates. This work may resolve some of the complexities of carbohydrate/glucose metabolic heterogeneity amongst different vertebrates and may provide a reference for the treatment of diabetes and for applications in the aquaculture industry.
葡萄糖作为大多数哺乳动物的主要能量来源发挥着关键作用，但它在鱼类中的重要性似乎很有限，这种现象似乎只存在于糖尿病患者身上。为了更好地理解鱼类中观察到的这种奇怪表型，世界各地的几个实验室都做出了重要努力。然而，碳水化合物/葡萄糖代谢的机制惊人地复杂。为什么鱼类和哺乳动物的基础血糖不同，以及不同生物之间的碳水化合物代谢有何不同，这些在很大程度上仍是未知领域。利用具有模式脊椎动物的比较系统生物学来探索鱼类代谢已成为揭示隐藏在体内机制的必要方法。
在这项研究中，我们首先构建了一个数据库，其中包含来自 Danio rerio、Xenopus tropicalis、Gallus gallus、Mus musculus 和 Homo sapiens 基因组的 791593523666 和 698 个碳水化合物/葡萄糖代谢基因，我们数据库中的大多数这些基因被预测编码在特定反应中发挥作用的特定酶；其中超过 57%与人类 2 型糖尿病有关。然后，我们系统地比较了这些基因，发现这五个物种中有超过 70%的碳水化合物/葡萄糖代谢基因是保守的。有趣的是，有 4 个斑马鱼特有的基因（si:ch211-167b20.8、CABZ01043017.1、socS9 和 eif4e1c）和 1 个人类特有的基因（CALML6）可能改变其相应物种的葡萄糖利用。有趣的是，这 5 个基因都是碳水化合物调节因子，但参与胰岛素调节途径的是酶本身。最后，为了方便使用我们的数据集，我们构建了一个葡萄糖代谢数据库平台（http://101.200.43.1:10000/）。
本研究首次系统地从基因组水平上研究了碳水化合物/葡萄糖代谢。经过详尽的分析，我们发现大多数代谢基因在脊椎动物中是保守的。这项工作可能解决了不同脊椎动物之间碳水化合物/葡萄糖代谢异质性的一些复杂性，并为糖尿病治疗和水产养殖应用提供了参考。
