Regulation of Energy Balance and Intestinal Function in Ancient Fishes

能量平衡的适当调节对地球上的所有生命都是至关重要的，在多细胞生物体中，能量平衡的部分实现是通过一系列激素释放到循环系统中，这些激素控制营养物质在肠道中的吸收，然后由有机体分配、储存或使用。胰腺B细胞释放的胰岛素对人类血糖的调节可能是这方面研究最深入的例子。在古代鱼类中，激素如何调节营养的吸收、储存和/或使用在很大程度上是未知的。因为活化石的弹性鳃(鲨鱼、溜冰鞋和鲟鱼)和鲟鱼是解决我研究计划的长期目标的很好的模型，也就是了解胰岛素和皮质类固醇等激素的功能是如何在脊椎动物中进化的。有三个短期目标的主要研究领域，旨在了解：1)控制激素释放；2)激素调节整个肠道的营养吸收；3)激素控制肝脏的营养加工。主要的营养物质是葡萄糖；然而，鲟鱼，特别是棘鳍的代谢结构表明，酮在整个动物的能量平衡中也起着重要的作用。拟议的目标集中在调节棘鳃和鲟鱼胰岛细胞中胰岛素的释放，以及胰岛素、胰升糖素和GLP-1等血糖调节激素如何影响这些古老鱼类的肠道葡萄糖吸收。鲟鱼皮质醇和弹性肌特异性皮质类固醇1α-羟基皮质酮(1α-OHB)对这两类鱼肝脏中葡萄糖和酮的处理作用将进一步加深我们对这些鱼类应激反应的机制基础的理解。弹簧科的具体研究将检验肠道微生物群落在全身氮平衡中所起的作用，并测试新的假设，即通过一种相互作用的关系，组织细菌介导1α-OHB的合成，这是一种类固醇，在这一古老的鱼类群体中，1α-OHB是全身能量和氮平衡的中心。参与这项研究的HQP将获得整个动物生理学的所有级别的技术技能。研究旨在发现在包容性环境中控制复杂生理系统的调控机制的演变，通过社区参与、会议出席、合作和出版促进所有个人的成功。这项研究将极大地影响我们对比较内分泌学中研究最多的激素--胰岛素和皮质类固醇--的进化的理解。此外，世界各地的许多鲟鱼和棘鱼物种正面临灭绝的威胁；所产生的数据将用于在全球水族馆贸易和鲟鱼养护水产养殖中改进对鲟鱼的管理和养护工作。

Appropriate regulation of energy balance is of fundamental importance to all life on earth and is in part achieved in multi-cellular organisms by a suite of hormones released into the circulatory system that act to control uptake of nutrients across the intestine followed by, distribution, storage or use by the organism. Regulation of blood glucose in humans by insulin released from pancreatic B cells is perhaps the most intensively studied example of this. In the ancient fishes how hormones regulate uptake, storage and/or use of nutrients is largely unexplored. As living fossils' elasmobranchs (sharks, skates and rays) and sturgeons are excellent models to address the long-term goal of my research program that is, to understand how the function of hormones like insulin and corticosteroids have evolved in vertebrates. There are three primary areas of research with short term objectives aiming to understand: 1) control of hormone release; 2) hormonal regulation of nutrient uptake across the gut; and 3) hormonal control of nutrient processing by the liver. The primary nutrient of interest is glucose; however, metabolic organization in sturgeons and in particular, elasmobranchs, indicate ketones also play an important role in whole animal energy balance. Proposed objectives focus on the regulation of insulin release in the pancreatic islet cells of both elasmobranchs and sturgeon and how glucoregulating hormones such as insulin, glucagon and GLP 1 influence uptake of glucose across the gut in these ancient fishes. The action of cortisol in sturgeon and the elasmobranch specific corticosteroid, 1alpha-hydroxycorticosterone (1 alpha-OHB), on processing of glucose and ketones in the liver in both groups of fishes will further our understanding in the mechanistic underpinnings of the stress response in these fishes. Elasmobranch specific research will examine the role the intestine microbial community plays in whole body nitrogen balance and test the novel hypothesis that through a mutualistic relationship tissue bacteria mediate synthesis of 1alpha-OHB, a steroid that is central to whole body energy and nitrogen balance in this ancient group of fishes. HQP involved in this research will gain technical skills at all levels of whole animal physiology. Studies are designed to discover the evolution of regulatory mechanisms controlling complex physiological systems in an inclusive environment that promotes the success of all individuals through community involvement, conference attendance, collaboration and publication. The research will significantly impact our understanding of the evolution of perhaps the most studied hormones in comparative endocrinology; insulin and corticosteroids. Furthermore, many species of sturgeons and elasmobranchs are under threat of extinction around the world; data generated will be applied to improve management and conservation efforts for elasmobranchs in the global aquarium trade and conservation aquaculture of sturgeons.