Therefore in the brain, investigation of tissue energetics has the potential to provide sensitive assessment of changes in glucose metabolism resulting from experimental intervention. PET is a well-established tool for studying brain glucose metabolism. However, the radiation risks associated with PET scans, although small, are of concern especially in young healthy volunteers and when carried out repeatedly. 31P MRS, unlike PET, does not involve exposure to ionizing radiation and offers a safe and novel approach. Upon binding of insulin to its receptor, signal transduction begins with activation of the IR substrate complex and subsequent activation of phosphoinositide-3-kinase

Inhibitors,research,lifescience,medical (PI3-K) (Okada et al. 1994). This leads Inhibitors,research,lifescience,medical to translocation of GLUT4 to the plasma membrane (Zierath et al. 1996). McNay et al. (2010) has shown in animal models that local delivery of insulin to the hippocampus results in improved cognitive performance via PI3-K-dependent mechanisms

along with increased removal of glucose from the interstitium. Blockade of endogenous hippocampal insulin was found to impair insulin-mediated improvements in cognitive function. Patients with insulin resistance are known to have increased circulating levels of plasma FFAs (Fraze et al. 1985) and have also been found to have increased brain fatty acid uptake (Karmi et al. 2010). Increases in Inhibitors,research,lifescience,medical plasma FFAs using a lipid infusion model have been shown to inhibit insulin signaling via PI3-K-dependent mechanisms (Dresner et al. 1999) and reduce insulin-mediated glucose uptake in skeletal muscle (Dresner et al. 1999; Roden et al. 1999). Lipid

infusions and high fat diets have been extensively used to model Inhibitors,research,lifescience,medical insulin resistance. Furthermore, contrary to previously held beliefs, there are several recent reports showing that FFAs do in fact cross the blood–brain barrier in significant amounts (Rapoport et al. 2001; Hamilton and Brunaldi 2007; Mitchell et al. 2011). The validity of the model Inhibitors,research,lifescience,medical in brain studies is strengthened by McNay et al. Cilengitide (2010) work in animal models demonstrating that insulin resistance, induced using a high-fat diet model, was associated with impaired hippocampal function. The duration and increase in FFA levels achieved in this study are comparable with previous studies performed in skeletal muscle in which FFA-induced alterations in insulin signaling http://www.selleckchem.com/products/ldk378.html cascade protein expression were demonstrated on biopsy tissue (Dresner et al. 1999; Roden et al. 1999). In addition, these studies also demonstrated the consequent reduction in whole-body insulin-mediated glucose uptake using hyperinsulinemic–euglycemic clamp techniques, showing reduced glucose infusion requirements following lipid infusion. The standardized meal would have stimulated a small release of peripheral insulin.