Insulin Causes Hyperthermia by Direct Inhibition of Warm-Sensitive Neurons
| Autor: | Kevin Myashiro, Hartmuth C. Kolb, Kristina Holmberg, Jeffrey S. Dubins, Manuel Sanchez-Alavez, Luis F. Gomez, John R. Hadcock, Peter T. Buckley, James Eberwine, Joe Klaus, Jeanine Jochems, James Secrest, Jean Schaefer, Kayo Mitsukawa, Olivia Osborn, Izabella Klein, Bruno Conti, Tamas Bartfai, Iustin V. Tabarean |
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| Rok vydání: | 2009 |
| Předmět: |
Male
medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Hypothalamus Biology Body Temperature Injections Mice 03 medical and health sciences 0302 clinical medicine Adipose Tissue Brown Internal medicine Brown adipose tissue Internal Medicine medicine Animals Insulin Telemetry 030304 developmental biology Neurons 0303 health sciences Raphe Hyperthermia Induced Thermoregulation Preoptic Area Mice Inbred C57BL Preoptic area Metabolism medicine.anatomical_structure Endocrinology nervous system Original Article Neuron Thermogenesis 030217 neurology & neurosurgery |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | OBJECTIVE Temperature and nutrient homeostasis are two interdependent components of energy balance regulated by distinct sets of hypothalamic neurons. The objective is to examine the role of the metabolic signal insulin in the control of core body temperature (CBT). RESEARCH DESIGN AND METHODS The effect of preoptic area administration of insulin on CBT in mice was measured by radiotelemetry and respiratory exchange ratio. In vivo 2-[18F]fluoro-2-deoxyglucose uptake into brown adipose tissue (BAT) was measured in rats after insulin treatment by positron emission tomography combined with X-ray computed tomography imaging. Insulin receptor–positive neurons were identified by retrograde tracing from the raphe pallidus. Insulin was locally applied on hypothalamic slices to determine the direct effects of insulin on intrinsically warm-sensitive neurons by inducing hyperpolarization and reducing firing rates. RESULTS Injection of insulin into the preoptic area of the hypothalamus induced a specific and dose-dependent elevation of CBT mediated by stimulation of BAT thermogenesis as shown by imaging and respiratory ratio measurements. Retrograde tracing indicates that insulin receptor–expressing warm-sensitive neurons activate BAT through projection via the raphe pallidus. Insulin applied on hypothalamic slices acted directly on intrinsically warm-sensitive neurons by inducing hyperpolarization and reducing firing rates. The hyperthermic effects of insulin were blocked by pretreatment with antibodies to insulin or with a phosphatidylinositol 3–kinase inhibitor. CONCLUSIONS Our findings demonstrate that insulin can directly modulate hypothalamic neurons that regulate thermogenesis and CBT and indicate that insulin plays an important role in coupling metabolism and thermoregulation at the level of anterior hypothalamus. |
| Databáze: | OpenAIRE |
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