Divergent mechanisms, convergent phenotype: the comparative physiology of glucose and fructose oxidation in vertebrate nectarivores

不同的机制，趋同的表型：脊椎动物食蜜动物葡萄糖和果糖氧化的比较生理学

• 批准号: RGPIN-2015-06129
• 负责人: Welch, Kenneth
• 金额: $ 2.04万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613963
• 关键词: Divergent; mechanisms; convergent; phenotype; comparative

The optimal use and regulation of fuels in skeletal muscles is key to animal performance and energy homeostasis, and thus the fundamental biology and ecology of organisms. Remarkably little of interspecific variation has been described among vertebrates, however, and differences are poorly understood. My research program seeks to identify and characterize the distinct “solutions” that have evolved for fueling intense exercise and managing energy homeostasis in two groups of nectar-eating vertebrates. A great deal has been learned about patterns of fuel use in exercising muscles of humans and other terrestrial mammals. All non-flying mammals apparently have similar capacities for the use of circulating sugars. Ingested glucose only partially fuels muscle activity and muscles make little direct use of fructose. However, these conserved fuel use patterns cannot be universal. Hummingbirds and nectar bats exhibit some of the highest aerobic metabolic rates of any vertebrates when hovering. My research has shown that these nectarivores can fuel most or all of hovering flight using ingested sugar. Evidence now suggests that these animals may even directly utilize fructose as readily as glucose in exercising muscles, a feat no other group of vertebrates can achieve. Yet, little is known regarding how this rapid transport, uptake, and oxidation of sugars occurs and is regulated. Most exciting, hummingbirds and bats likely employ fundamentally different mechanisms. Nectar bats, like all mammals, express glucose transporter protein 4 (GLUT4) in muscle, a critically important component of the sugar uptake and blood glucose management system. Hummingbirds, however, lack GLUT4. Rapid sugar transport into muscles must be regulated differently in each group. I will characterize the functional enhancements that permit the rapid uptake and oxidation of sugars in muscles in these groups, highlighting differences between them related to their independent evolution. Three steps are believed to be key regulation points for the uptake and oxidation of sugar by muscle: 1) absorption of dietary sugar, delivery, via the circulatory system, to the extracellular fluid surrounding working muscles, 2) transport of sugars into the sarcoplasm, and 3) phosphorylation of sugars by a hexokinase (HK) enzyme. I will 1) use non-invasive techniques to determine the relative kinetics, and partitioning of, glucose and fructose oxidation in hummingbirds and nectar bats; 2) quantify capacities for phosphorylation and oxidation of each sugar in muscle fibers directly (step 2); 3) quantify tissue affinities and capacities for uptake of glucose and fructose (step 3). These studies will characterize the potentially novel mechanisms hummingbirds and nectar bats employ to both tolerate and exploit their sugar-rich diet and extreme fluctuations in blood sugar. This program will train 3 PhD, 4 MSc, and 10 undergraduate students.

骨骼肌中燃料的最佳使用和调节是动物生产性能和能量稳态的关键，因此也是生物的基本生物学和生态学。然而，在脊椎动物中，种间变异的描述非常少，而且对差异的了解也很少。我的研究项目旨在识别和描述两组食蜜脊椎动物中为剧烈运动提供燃料和管理能量稳态而进化出的不同“解决方案”。