EXERCISE AND GLUCOSE REGULATION IN OLDER WOMEN

在这项提案中，我们计划结合社区、临床和实验室的措施，以更清楚地了解特定的细胞、激素、人体测量和代谢适应在成功衰老中维持功能的作用。为了实现这些目标，我们计划对绝经后妇女进行研究，这些妇女拥有最先进的临床、实验室和创新的实用培训技术，专门针对2型糖尿病的机制和先兆。这项拟议研究的总体目的是确定有氧运动对改善老年女性葡萄糖代谢的影响，并确定这种关系中的关键因素。根据这一建议，我们计划：1)在体重正常、但有或没有过度内脏-皮下肥胖的老年女性中，建立胰岛素抵抗的几种激素和脂质相关机制和调节因子(例如，肌肉脂蛋白脂酶(LPL)mRNA和蛋白质含量、皮质醇对身体挑战的反应、胰岛素刺激的肝脏葡萄糖产生(HGP)的减弱抑制和血浆游离脂肪酸浓度)水平的横断面差异；2)确定9个月高强度或中等强度(但等量热量输出)的有氧运动训练对迷你蹦床上这些激素和血脂相关变量以及随后胰岛素刺激的全身葡萄糖处置的影响；3)确定训练适应程度是否因训练强度和/或内脏脂肪库的大小而异。据我们所知，这在任何使用这些技术的老年人群中都没有得到证明。通过确定这些研究变量中与衰老相关的变化以及由此导致的血糖调节缺陷是否会因运动而改变，我们可以洞察与老年人功能受损相关的因素以及适应发生的程度。此外，这些信息还可以用来为老年人设计安全有效的社区锻炼计划，重点是在衰老过程中维持血糖调节和整体功能。

In this proposal we plan to combine community-, clinical-, and laboratory-based measures to understand more clearly the role of specific cellular, hormonal, anthropometric, and metabolic adaptations that maintain function in successful aging. To accomplish these goals, we plan to study postmenopausal women with state-of-the-art clinical, laboratory, and innovative and practical training techniques specific to mechanisms and precursors of type 2 diabetes. The overall purpose of the proposed study is to determine the impact of aerobic exercise on improvements in glucose disposal in older women and to identify key factors in this relationship. With this proposal we plan: 1) to establish cross-sectional differences in levels of several hormone- and lipid-related mechanisms and modulators of insulin resistance (e.g., muscle lipoprotein lipase (LPL) mRNA and protein content, cortisol response to a physical challenge, attenuated suppression of insulin-stimulated hepatic glucose production (HGP) and plasma concentrations of free fatty acids) in older women of normal body weight, but with and without excess visceral-to subcutaneous abdominal adiposity; 2) to determine the effects of 9 months of aerobic exercise training of either higher- or moderate-intensity (but equivalent caloric output) on the mini-trampoline on these hormone- and lipid-related variables and consequent insulin-stimulated whole-body glucose disposal; and 3) to determine whether the degree of adaptation with training varies by training intensity and/or size of the visceral fat depot. To our knowledge, this has not been demonstrated in any older population using these techniques. By determining whether the aging-related changes in these study variables and consequent deficit in glucose regulation are altered by exercise, we can provide insight into the factors associated with compromised function in older age and the extent to which adaptation occurs. Moreover, this information can then be used to design safe and effective community-based exercise programs for older people that focus on the maintenance of glucose regulation and overall function in aging.