Pancreatic Hormones and Their Functions in Agnathans and Teleost Fishes

几个世纪以来，鱼类一直是实验研究的对象，但它们作为实验模型的作用，可以代替传统的实验室温血动物，尤其是在最近才得到加强。代表性的鳗类（七鳃鳗或盲鳗）和硬骨鱼（鲑鱼、鳟鱼、鲶鱼）将被用于研究胰腺激素对代谢和生长的调节、它们之间的相互作用以及它们与生长激素和胰岛素样生长因子的相互作用。该项目的具体目标是：1)开发新的同源放射免疫测定法或酶联免疫测定法来测量七鳃鳗的胰岛激素；2)继续评估鲑鱼、鳟鱼和七鳃鳗在不同生命周期阶段和不同饲养方式下血浆和内分泌胰腺中的胰腺激素特征；3)测定从胰岛（主要产生部位）和肝脏（胰腺激素的重要目标和主要破坏部位）流出的血液中胰腺激素的水平；评估禁食和饲养动物在这些模式下激素含量的差异；4)研究来自肝脏不同部位的细胞在遇到不同水平的激素时是否存在代谢分化，并利用分离的肝细胞作为体外实验系统，研究调节能量储存的胰高血糖素家族肽的作用；5)研究主要合成代谢激素胰岛素在不同发育阶段和不同喂养方式下与其靶点肝脏的特异性结合；6)研究七鳃鳗和鲑鱼内分泌胰腺中异常丰富的“大”生长抑素是否具有特殊的生理意义。预期的结果将有助于更好地理解激素对营养和生长的调节，并扩展我们对脊椎动物胰腺激素功能进化的认识。

Fish have served as objects of experimental research for several centuries, however their role as an experimental model, which can substitute for conventional laboratory warmblooded animals has been enhanced particularly in recent times. Representative agnathans (lamprey or hagfish) and teleost fish (salmon, trout, catfish) are to be used in studies of the regulation of metabolism and growth by pancreatic hormones, their interaction with each other and with growth hormone and insulin-like growth factor. Specific objectives of the project are: 1) to develop new homologous radioimmunoassays or enzyme- linked immunoassays for measurement of the islet hormones in lampreys; 2) to continue an assessment of the profiles of pancreatic hormones in plasma and endocrine pancreas of salmon, trout and lamprey at different stages of their life cycles and kept under different feeding regimes; 3) to determine the levels of pancreatic hormones in the blood outflow from the pancreatic islets (major producing sites) and from the liver, (important target and main place for destruction of the pancreatic hormones); to evaluate the differences in the hormonal contents in fasting and feeding animals with respect to these patterns; 4) to examine whether the cells from different parts of liver, encountering different levels of hormones are metabolically differentiated and to employ isolated hepatocytes as an experimental in vitro system for investigation of the effects of glucagon-family peptides, which regulate energy stores; 5) to study specific binding of the major anabolic hormone, insulin to its target, the liver, at different developmental stages and under different feeding regimes; 6) to investigate whether the unusual abundance of "big" somatostatins in the endocrine pancreas of lamprey and salmon has any particular physiological significance. The expected results will contribute to better understanding of hormonal regulation of nutrition and growth as well as extend our knowledge of functional evolution of pancreatic hormones in vertebrates.