GLUCOSE/INSULIN DYNAMICS OF HIGHLY VARIABLE METABOLIC STATES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本方案参与UVA在研究闭环血糖控制器的前景中将系统生物学应用于葡萄糖/胰岛素动力学的日益努力。我们建议调查在高度不稳定的生理状态下的葡萄糖/胰岛素平衡和动态，即：（i）体力活动，低强度和高强度;（ii）营养摄入。这两种情况在日常生活中非常常见，并且已被确定为闭环葡萄糖控制的主要缺陷。因此，拟定的研究计划包括对摄入和注射葡萄糖期间以及体力活动期间的葡萄糖/胰岛素动力学进行基于GCRC的研究。具体而言： 初步阶段将研究低强度运动对T1 DM患者MMGK参数的影响。对已经收集的数据进行建模将允许识别葡萄糖/胰岛素网络的哪一部分受到身体活动的影响，从而导致MMGK的修改以允许运动时段。 第一阶段将使用初步阶段的结果来研究低强度和高强度运动对健康年轻人葡萄糖/胰岛素网络的影响。将使用类似的实验设计，以比较T1 DM和健康患者。将增加一个高强度运动期，以研究反调节现象的影响。 第2阶段将研究由于摄入营养素而引起的葡萄糖/胰岛素网络的变化。使用最小模型方法，我们将研究注射和摄入葡萄糖之间的差异，从而对肠促胰岛素效应进行建模。这一阶段将导致CPMM的修改，以适用于真实的生活场景，即进餐而不是静脉注射葡萄糖。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This protocol participates to an increasing effort at UVA to apply system biology to the glucose/insulin kinetics in the prospect of studying a closed loop blood glucose controller. We propose to investigate the glucose/insulin equilibrium and dynamics in health during highly unstable physiological states, namely: (i) physical activity, both low and high intensity; (ii) nutrient ingestion. Both situations are very common in daily life and have been identified as major draws back in closed loop glucose control. Consequently the proposed research plan includes a GCRC-based investigation of the glucose/insulin dynamics during ingested and injected glucose as well as during physical activity periods. Specifically: The preliminary phase will investigates the effect of low intensity exercise on the MMGK parameters in T1DM patients. Modeling of already collected data will allow to identify which part of the glucose/insulin network are affected by physical activity, thus leading to a modification of the MMGK to allow exercise periods. Phase 1 will use results from the preliminary phase to study the effect of low and high intensity exercise on the glucose/insulin network in healthy young adults. A similar experimental design will be used, allowing for comparison between T1DM and healthy patients. An high intensity exercise period will be added to study the influence of counter regulatory phenomena. Phase 2 will investigates the modifications in the glucose/insulin network due to the ingestion of nutrient. Using a minimal model approach we will investigate the difference between injected and ingested glucose, thus modeling the incretin effect. This phase will lead to modification of the CPMM to be applicable to real life scenario, namely a meal instead of IV injection of glucose.