Thermorégulation | EPFL Graph Search

La thermorégulation est l'ensemble des mécanismes qui permet à un organisme ou à un système de se maintenir à une température souhaitée. Elle est le résultat de production et de déperdition d'énergie thermique. Dans le monde du vivant, on distingue les organismes homéothermes des organismes poïkilothermes. Les poïkilothermes sont des organismes dont la température interne varie avec la température de leur environnement, contrairement aux homéothermes qui disposent d'une thermorégulation efficace permettant un contrôle de leur température. La thermorégulation se fait par la thermolyse (perte de chaleur) et la thermogenèse (production de chaleur). Importance La vie est un phénomène complexe dont la base est un ensemble de réactions chimiques et de phénomènes physiques. Or, la température a une influence capitale sur les réactions chimiques (voir l'article Thermochimie) :

une réaction n'est possible que dans une gamme de température donnée ;
la cinétique chimique dépend

JewelPUMP (TM) by Debiotech S.A.: Insulin Temperature Measurement Study

Adrien De Muralt

For type 1 Diabetes, insulin injection therapy is the most used treatment today, and insulin pumps are surely the most accurate therapeutic strategy. The insulin use temperature has to not exceed 37°C to prevent unwanted degradation and loss of function. The JewelPUMP (TM) developed by Debiotech S.A., is directly patchable on the skin patient and was the first of its type to integrate a temperature sensor. However, it is unacceptable to place this sensor in direct contact to the insulin, regarding sterility integrity and the actual design of the device. The present study aimed to define how the insulin temperature could be predicted based on the values recorded by this sensor. Two setups were designed to assess the problem in vivo and in vitro: the first includes a patient wearing the pump under different environmental conditions, and the second is based on an electrical thermoregulation system mimicking the human body and its environment by placing it in a climatic chamber. The in vivo setup allowed us to propose a specific Curve Fitting Model (CFM) matching to the real data, based on heat transfer laws and assessing the dynamic of the problem. Two main heat sources were identified: the patient body and the ambient air around the pump. We determined that the insulin restrained in the reservoir reacts more to the body temperature Trbody than to the ambient temperature Trout; inversely, the sensor is more impacted by Trout than by the Trbody. At steady state, the presence of an offset between the sensor and the real insulin temperatures was confirmed. This offset is positive when Trout > Trbody, and negative when Trout < Trbody. Under ideal conditions, if Trout and Trbody are constant, a constant offset was supposed. The behaviour of this offset was investigated with the in vitro setup. The in vitro setup allowed us to monitor accurately the different parameters of the problem. We validated that our thermoregulation system, based on a Peltier system, was able to mimic the thermal behaviour of the human body and the human skin in vitro. Regarding the dynamic, as for in vivo experiments, the proposed CFM matched well to the obtained data. At steady state, the offset was always positive for Tlout > Tlbody, negative for Tlbody > Tlout, and equal to 0 when Tlout=Tlskin corresponding to the equilibrium of our thermal system. The offset after stabilization (Offsetlstab.) was determined as to be a constant exhibiting a dependence on the difference between Tlout and Tlbody. For a fixed Tlbody, the Offsetlstab. increases with Tlout; for a fixed Tlout, the Offsetlstab. increases with Tlbody. This offset ranges between -5°C and +5°C. Based on in vivo and in vitro data analysis, we were able to affirm that it is impossible to predict the real insulin temperature, based only on the single temperature sensor. We identified two main solutions in order to solve this problem. The first consists to placed a different sensor closer to the insulin solution. The second is based on the idea to add a second sensor somewhere else in the JewelPUMP (TM).

2011

Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons

David Genoux

The physiological contribution of glucose in thermoregulation is not completely established nor whether this control may involve a regulation of the melanocortin pathway. Here, we assessed thermoregulation and leptin sensitivity of hypothalamic arcuate neurons in mice with inactivation of glucose transporter type 2 (Glut2)-dependent glucose sensing. Mice with inactivation of Glut2-dependent glucose sensors are cold intolerant and show increased susceptibility to food deprivation-induced torpor and abnormal hypothermic response to intracerebroventricular administration of 2-deoxy-D-glucose compared to control mice. This is associated with a defect in regulated expression of brown adipose tissue uncoupling protein I and iodothyronine deiodinase II and with a decreased leptin sensitivity of neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons, as observed during the unfed-to-refed transition or following i.p. leptin injection. Sites of central Glut-2 expression were identified by a genetic tagging approach and revealed that glucose-sensitive neurons were present in the lateral hypothalamus, the dorsal vagal complex, and the basal medulla but not in the arcuate nucleus. NPY and POMC neurons were, however, connected to nerve terminals from Glut2-expressing neurons. Thus, our data suggest that glucose controls thermoregulation and the leptin sensitivity of NPY and POMC neurons through activation of Glut2-dependent glucose-sensing neurons located outside of the arcuate nucleus.-Mounien, L., Marty, N., Tarussio, D., Metref, S., Genoux, D., Preitner, F., Foretz, M., Thorens, B. Glut2-dependent glucose-sensing controls thermoregulation by enhancing the leptin sensitivity of NPY and POMC neurons. FASEB J. 24, 1747-1758 (2010). www.fasebj.org

2010

Thermal microsensors for in vitro and in vivo monitoring of chemical and biological processes

Rima Padovani

Metabolism is a highly coordinated biochemical cellular activity indispensable for sustaining life, and is often related to mitochondrial functioning. Innovative technological approaches allowing the study of the thermal signature of chemical and metabolic processes are presented in this thesis. In particular, two solutions are proposed: (i) a nanocalorimetric platform enabling measurements of biochemical heat production in vitro, and (ii) a method for localized in vivo temperature measurements in mice using implantable miniaturized sensors. First, the design and development of the nanocalorimetric platform is presented. In particular, this platform is built around a commercial thermopile-based sensor chip, on which an open-well reservoir holding a sample with a volume of a few tens of microliter is directly positioned. Both components are embedded into an isothermal housing providing an excellent temperature stability (± 1 mK), which is a prerequisite for accurate heat power measurements. Furthermore, the platform is characterized by a fast thermalization time to the target temperature (less than 30 minutes) and a fast sensing response time (a few seconds). Numerical simulations, which allowed the optimization of the platform design, are also reported. Electrical calibration of the platform was carried out using resistive heaters positioned either on the sensor chip or in the sample reservoir. A heat power limit of detection of 70 nW was estimated. Then, two reactions for the validation of the nanocalorimetric platform were investigated: (i) the mixing of 1-propanol in water, and (ii) the oxidation of glucose catalyzed by glucose oxidase. The results showed good agreement with literature, confirming that our versatile platform may be applied to many thermochemical studies, including thermodynamic analysis and kinetic reaction analysis. Furthermore, localized in vivo temperature measurements in mice by means of implantable miniaturized sensors are presented. The aim was to monitor mouse metabolism during cold exposure, and to record possible temperature differences between the body temperature measured in the abdomen and the temperature of the brown adipose tissue (BAT) situated in the interscapular area. This approach is of biological interest as it may help unravelling the question whether biochemical activation of BAT is associated with local increase in metabolic heat production. Specifically, the preparation and calibration of miniaturized thermistor sensors are reported and the surgical procedure is also described. Temperature measurements, carried out on mice during cold exposure (6 °C) for a maximum duration of 6 hours, are presented and analyzed. Control measurements with a conventional probe confirmed the good performance of the implanted sensors. Moreover, analysis of the experimental results allowed the identification of two different mouse phenotypes, distinguishable in terms of their metabolic resistance to cold exposure. This difference was investigated from the thermal point of view by computational simulations. A simple physical model of the mouse body allowed to reproduce the global evolution of hypothermia and to explain qualitatively the temperature difference between abdomen and BAT locations. While with this approach, we have demonstrated the importance and feasibility of localized temperature measurements on mice, further optimization of this technique is foreseen to better identify local metabolism variations.