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

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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.