Annual Report of Activities CNC 2008 - Center for Neuroscience and ...
Annual Report of Activities CNC 2008 - Center for Neuroscience and ...
Annual Report of Activities CNC 2008 - Center for Neuroscience and ...
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Intermediary Metabolism | Head: John JonesObjectivesIn settings <strong>of</strong> insulin resistance <strong>and</strong> non‐insulindependent(Type 2) diabetes, the loss <strong>of</strong> glucose<strong>and</strong> lipid homeostasis results in secondarycomplications such as heart disease <strong>and</strong> blindness.To underst<strong>and</strong> the precise effects <strong>of</strong> substrateimbalances <strong>and</strong> secondary complications on themetabolic function <strong>of</strong> liver, heart <strong>and</strong> brain, we aredeveloping detailed yet practical stable‐isotopetracer measurements <strong>of</strong> intermediary metabolismin both humans <strong>and</strong> in animal models <strong>of</strong> diabetes.These assays are designed to quantify fluxesthough the principal mammalian pathways <strong>of</strong>intermediary metabolism including glycolysis,gluconeogenesis, glycogen synthesis, pentose cycle,lipogenesis <strong>and</strong> the Krebs cycle. Thesemeasurements are providing new insights abouthow intermediary metabolism is modified in theliver, heart <strong>and</strong> brain in the setting <strong>of</strong> insulinresistance, hyperglycemia <strong>and</strong> diabetes.Main Achievements1. Defining the effects <strong>of</strong> transaldolase exchangeactivity on tracer measurements <strong>of</strong> hepaticgluconeogenesis <strong>and</strong> indirect pathway fluxes.2. Development <strong>of</strong> a user‐independent Bayesiananalysis <strong>for</strong> 2H NMR spectra derived from urinaryglucuronide.3. Correlating noninvasive tracer measurements <strong>of</strong>hepatic glycogenolytic fluxes in Type 1 diabetespatients with direct in vivo measurement <strong>of</strong> hepaticglycogen levels by localized 13C magneticresonance spectroscopy.4. Quantifying plasma glucose 2H‐enrichment frommicroliter blood samples via LC‐MS.5. Preservation <strong>of</strong> metabolic fluxes in hearts usingcardioplegic preservation solutions.Characterization <strong>of</strong> mitochondrial bioenergetics<strong>and</strong> immunological pr<strong>of</strong>iles in ischemia <strong>and</strong>ischemia/reperfusion.6. Evaluation <strong>of</strong> metabolic fluxes in hippocampus<strong>and</strong> protection <strong>of</strong> cognitive per<strong>for</strong>mance bycaffeine. Correlation <strong>of</strong> energy metabolism withadenosine receptor‐mediated neuroprotection.70
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