Neuronal Glutamate Synthesis and Degradation

Dr. LaNoue and her colleagues are engaged in an evaluation of factors that control the de novo synthesis and utilization of glutamate in the brain and retina. Glutamate is the most important neurotransmitter in the brain. About half the total cerebral pool of glutamate is used and re-synthesized every 10 minutes. Several drugs, which are known to alter the rate of resynthesis of glutamate specifically in neural tissues, have important influences on epilepsy, chronic pain, and, possibly neurodegeneration. Dr. LaNoue's laboratory is using radioisotopic techniques to map pathways of neuronal glutamate synthesis and degradation and to identify new drug targets for altering glutamate turnover.

The Role of Adenosine Receptors in Muscle Insulin Resistance

Dr. LaNoue's laboratory is also involved in studies of diabetes and insulin resistance in a strain of genetically obese rats. The laboratory has observed that an A2b adenosine receptor antagonist is able to partially reverse the insulin resistance characteristic of these obese animals without inducing a change in their percent body fat. By independently varying insulin levels, fatty acid levels, and A2b adenosine receptor antagonist levels while measuring radiolabeled glucose uptake in the muscles of these animals, Dr. LaNoue hopes to identify the cause of the insulin resistance and to learn how the A2b adenosine receptor antagonist ameliorates the problem. Measurements of the extent of activation of components of the insulin signaling pathway such as insulin receptor kinase activity, insulin receptor substrate 1 activation, and phosphatidylinositol-3-kinase activity will aid in interpretation of the data obtained.