Increased GLUT3 expression may meet this demand, as has been demonstrated in response to chronic increases in neuronal glucose requirements

(Vannucci 1994). However, Choeiri et al. (2005) found that acutely increased demand associated with cognitive activity and training tasks was associated with increased hippocampal GLUT1 expression, Inhibitors,research,lifescience,medical thus allowing increased glucose uptake from the circulation to the interstitial fluid. GLUT3, however, did not increase. Therefore, additional transport mechanisms may need to be inducted to meet acute increases in neuronal glucose requirement during cognitive activity. Insulin-mediated glucose uptake occurs by promoting rapid and substantial translocation of GLUT4 from sequestered intracytoplasmic pools to the plasma membrane (Mueckler 1994) within minutes of insulin binding to the receptor. Insulin signaling therefore provides a mechanism able to rapidly stimulate high-affinity Inhibitors,research,lifescience,medical additional glucose uptake. These kinetic characteristics would fit with a role for neuronal insulin signaling in facilitating rapid stimulated glucose Inhibitors,research,lifescience,medical uptake according to neuronal activity. This is also

consistent with Hori’s demonstration of excitatory neurotransmitter-induced insulin signaling cascade protein expression in the postsynaptic density (Hori et al. 2005). We propose that this insulin-stimulated transport may EGFR cancer provide a mechanism for meeting the increase in glucose requirement during cognitive activity. To investigate this link between cognitive impairment

and insulin Inhibitors,research,lifescience,medical resistance, we applied a lipid infusion model of insulin resistance (Dresner et al. 1999; Roden et al. 1999) to study hippocampal tissue energetics in healthy volunteers. Tissue energetics were investigated by assessing high-energy phosphate levels using phosphorus magnetic resonance spectroscopy (31P MRS). Intracellular energy Inhibitors,research,lifescience,medical is produced and transported in the form of adenosine triphosphate (ATP). A reduction in glucose supply would result in reduced ATP production. The ATP molecule is readily converted to phosphocreatine (PCr) to provide an intracellular buffer store, which can be readily hydrolyzed to produce Farnesyltransferase ATP. The PCr/ATP ratio therefore provides an index of cellular energy availability, and a reduction in the PCr/ATP ratio reflects reduced ATP production relative to concurrent energy consumption. Aim Inhibition of the insulin signaling mechanisms that putatively facilitate increased glucose uptake during cognitive activity would lead to relative insufficiency of neuronal energy substrate. This energy deficit would be reflected as a reduction in the hippocampal PCr/ATP ratio. The aim of this study was to determine whether hippocampal energetics during cognitive activity were impaired in a human experimental model of insulin resistance.