Sex differences in the glucoregulatory response to acute and recurrent exercise.

当血糖快速或逐渐降低时，中枢和外周葡萄糖神经传感器通过神经激活葡萄糖反调节（GCR）激素的释放来检测和刺激肝脏葡萄糖的分泌。据报道，这些葡萄糖感应神经元激活的血糖阈值可以通过先前的运动而改变。运动将GCR激活的血糖阈值降低到较低的葡萄糖水平的机制被称为运动相关性自主神经衰竭（EAAF）。有研究表明，先前的全身性激素升高会影响应激引起的血糖阈值的变化，而另一些人则认为，运动介导的脑代谢改变会导致这些中枢神经受体的短暂失活。虽然大多数关于运动对葡萄糖调节影响的研究都是在男性身上进行的，但已经证明，运动后GCR激素分泌和葡萄糖产生的差异在性别之间是不同的。目前尚不清楚运动对大脑代谢和全身激素的反应是否能解释这些差异，也不清楚血糖阈值的变化是否会增加不同性别的EAAF风险。最后，运动训练和高血糖以及运动方式对EAAF的影响尚未研究。我的研究计划的目标是：1)检查性别特异性的激素和大脑代谢对急性运动的反应。2)阐明激素和脑代谢反应在EAAF中的性别特异性作用。3)确定运动方式和训练、慢性高血糖对急性运动后性别特异性GCR反应以及EAAF的影响。本研究项目将使用实验大鼠血糖应激模型，包括有氧运动和/或阻力运动。在雌性大鼠中，我们将在发情周期的每个阶段检查运动，以研究性激素波动对急性运动和反复运动中EAAF发作时GCR反应的影响。将完成药物和手术干预实验，以增强大脑代谢和全身激素对运动的反应，而先前的运动训练（不同模式）和/或慢性高血糖将被用来阐明这些因素如何影响急性运动和反复运动期间EAAF的GCR反应。这一新的研究领域将更好地理解运动过程中葡萄糖稳态的性别差异，同时提高我们对运动方式、运动训练后和慢性高血糖之间的差异的认识。这项工作建立在我们实验室不断努力的基础上，以科学发现生物体的生物功能，培养高素质的人才和他们在自然科学领域的独特技能。

In response to rapid or gradual reductions in blood glucose, central and peripheral glucose neural sensors detect and stimulate the secretion of hepatic glucose through the neural activated release of glucose counterregulatory (GCR) hormones. It has been reported that the glycemic thresholds by which these glucose-sensing neurons activate can be altered by prior exercise. Termed Exercise-associated autonomic failure (EAAF), the mechanisms by which exercise shifts the glycemic thresholds for GCR activation to lower glucose levels are not known. Prior elevation of systemic-hormones influencing a stress-induced shift of the glycemic thresholds has been suggested, while others propose that exercise-mediated alterations in brain metabolism lead to a transient inactivation of these central neural receptors. While the majority of studies examining the influence of exercise on glucose regulation have been conducted in males, it has been demonstrated that differences in GCR hormone secretion and glucose production in response to exercise is different between sexes. It is not clear if brain metabolic and systemic-hormonal responses to exercise explain these discrepancies, and whether the shifts in glycemic thresholds may increase the risk of EAAF differently between sexes. Lastly, the impact of exercise training and hyperglycemia, as well as exercise modality on EAAF have not been investigated. The objectives for my research program are: 1) to examine the sex-specific hormonal and brain metabolic responses to acute exercise. 2) To elucidate the sex-specific role of hormonal and brain metabolic responses in EAAF. 3) To determine the influence of exercise modality and training, and chronic hyperglycemia on the sex-specific GCR response to acute exercise, as well as EAAF. This research program will use an experimental rat model of glycemic stress, consisting of aerobic and/or resistance exercise. In female rats, exercise will be examined at each stage of the estrous cycle to investigate the influence of sex hormonal fluctuations on the GCR response to acute exercise and EAAF onset during recurrent exercise. Pharmacological and surgical intervention experiments will be completed to augment brain metabolic and systemic-hormonal responses to exercise, while prior exercise training (with different modalities) and/or chronic hyperglycemia will be employed to elucidate how these factors influence the GCR response to acute exercise and EAAF during recurrent exercise. This novel area of study will provide a better understanding of sex-related differences in glucose homeostasis during exercise, while advancing our knowledge of how they differ between exercise modalities, following exercise training and chronic hyperglycemia. This work builds on our laboratory's continuing effort towards scientific discovery in biological function in living organisms and the training of highly qualified personnel and their unique skills acquisition in natural sciences field.