Implantable sensors allow continuous monitoring of blood glucose levels in freely moving mice. This technology is potentially transformative for research on diabetes and metabolism, and will be even more powerful in combination with metabolic cages, which will allow glucose fluctuations to be compared to eating, movement, and metabolic rate. The telemetry system can alternately be used for monitoring blood pressure and heart rate, resulting in a drastic improvement over the standard ?tail cuff? method. Telemetry has inherent advantages, including avoiding stress to the animals, improving the quality and quantity of data that can be collected, and decreasing animal usage. However, in this case, the advantages go far beyond these points, as experiments that were not previously possible can be performed. These include testing whether fluctuations in blood sugar acutely influence metabolic rate, and how minute-to-minute changes blood sugar are related to meals and movement. The proposed instrumentation allows detection of circadian rhythms in glucose and blood pressure, and comparison to rhythms in metabolic rate and locomotor activity. It allows glucose variability to be considered independently from the average concentration ? this approach has already been shown to detect early stage metabolic disease in humans, but was not previously possible in rodents. It also allows monitoring glucose under conditions where it would not otherwise be measurable, such as during hyperglycemic episodes following hemorrhagic shock; in this model, mice are already at the limit of blood loss that can be sustained, making it impossible to collect more blood for glucose measurement unless the experiment is immediately terminated. Similarly, during septic shock, mice are though to experience vascular collapse that could be detected with blood pressure telemetry, but this is otherwise impossible to demonstrate as mice cannot be immobilized and heated indefinitely for tail cuff measurements. Sleep disorders can have dramatic consequences for metabolic health that are only beginning to be explored, but blood glucose can't be measured without awakening and stressing the animals; telemetry completely avoids this issue and makes it possible to study minute-to-minute changes in glucose during sleep-wake cycles. These are just a few of the potential applications for what is likely to become the gold standard for metabolic studies over the next 5-10 years. The Mouse Physiology, Phenotyping, and Metabolism Core (MPPMC) of Penn's Diabetes Research Center, where the proposed instrumentation would be housed, has a long history of assisting NIH-funded researchers at Penn, within the greater Philadelphia area, and across the country. Multiple surgeons who are capable of implanting telemetry probes are available to assist with projects, and the core has extensive experience operating and interpreting the output from metabolic cages as well as general expertise in metabolism and glucose homeostasis. Thus, the requested instruments would make this powerful combination of technologies available to many potential users, including the immediate users listed in this application.
Much of our understanding of metabolic diseases has been learned through studying and manipulating metabolism in rodents. However, many of the most relevant parameters, including blood glucose levels and blood pressure cannot be assessed without invasive and stressful procedures that compromise the data quality and preclude measuring multiple variables at the same time. The proposed instrumentation will allow simultaneous recording of key metabolic parameters in undisturbed mice, improving data quality, reducing the number of animals required for experiments, and allowing researchers to test hypotheses about the relationships between variables that could not previously be addressed.
