RUI: Glucose Production and Disposal During Long Term Fasting Northern Elephant Seals.

RUI：北象海豹长期禁食期间葡萄糖的产生和处理。

• 批准号: 0818018
• 负责人: Daniel Crocker
• 金额: $ 30.79万
• 依托单位: Sonoma State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0818018&HistoricalAwards=false
• 关键词: RUI; Glucose; Production; Disposal; During

A major challenge of long-term fasting is the provision of glucose for glucose-dependent tissues (e.g. central nervous system) while sparing protein in vital body organs. Seals provide an excellent system to investigate metabolic strategies during fasting because they undertake natural fasts during periods that elevate nutrient demands. Weaned northern elephant seals fast for 2-3 months, during which time physiological development supporting their diving ability occurs. Previous investigations in this system revealed a number of unique features of metabolism that differ from the traditional view of fasting adaptation. Despite efficient protein sparing, plasma glucose levels in elephant seals are high throughout the fast. Levels of glucose production fail to exhibit the suppression with fasting that is seen in other species. Breakdown of protein and fats provides only a small portion of this glucose production and, therefore, the source of this endogenous glucose production has not been identified. This research project will investigate glucose production and disposal during long-term natural fasts in northern elephant seals. Isotopic tracer techniques and respirometry will be combined to 1) examine the contribution of various substrates to glucose production 2) examine the metabolic strategies for glucose clearance 3) examine variation in fuel use over fasting period and 4) examine the activity of several key metabolic cycles that may regulate glucose production. This study will provide important information about the metabolic strategies that enable long-term fasting during development. Increased understanding of the novel features of carbohydrate regulation in fasting-adapted animals, including maintenance of high blood glucose while fasting, avoidance of ketoacidosis, protein sparing despite high rates of glucose production, and high rates of glucose disposal despite low insulin levels and insulin resistance can potentially inform our understanding of human pathologies of carbohydrate metabolism. This research will also promote research training and education to undergraduate and graduate students, especially underrepresented minority students, through participation in exciting research on a unique wildlife system.

长期禁食的一个主要挑战是为依赖葡萄糖的组织(如中枢神经系统)提供葡萄糖，同时节省身体重要器官中的蛋白质。海豹提供了一个很好的系统来研究禁食期间的新陈代谢策略，因为它们在营养需求增加的时期进行自然禁食。断奶的北方象海豹禁食2-3个月，在此期间，支持它们潜水能力的生理发育发生。以前对这个系统的研究揭示了一些独特的新陈代谢特征，这些特征不同于禁食适应的传统观点。尽管有效地节省了蛋白质，但在整个斋戒过程中，象海豹的血糖水平都很高。葡萄糖的产生水平没有表现出在其他物种中看到的禁食抑制作用。蛋白质和脂肪的分解只提供了葡萄糖产生的一小部分，因此，这种内源性葡萄糖产生的来源尚未确定。这项研究项目将调查北象海豹在长期自然禁食期间葡萄糖的产生和处置。同位素示踪技术和呼吸测量法将结合起来，1)检查各种底物对葡萄糖产生的贡献，2)检查葡萄糖清除的代谢策略，3)检查禁食期间燃料使用的变化，4)检查可能调节葡萄糖产生的几个关键代谢周期的活动。这项研究将提供有关在发育过程中实现长期禁食的代谢策略的重要信息。提高对禁食适应动物碳水化合物调节新特性的了解，包括禁食时维持高血糖，避免酮症酸中毒，高葡萄糖生成率下的蛋白质节制，以及低胰岛素水平和胰岛素抵抗时的高葡萄糖处理率，可能有助于我们理解人类碳水化合物代谢的病理。这项研究还将通过参与关于独特野生动物系统的激动人心的研究，促进本科生和研究生，特别是未被充分代表的少数民族学生的研究培训和教育。