GLUCOSE/INSULIN DYNAMICS OF HIGHLY VARIABLE METABOLIC STATES

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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.