The goal of this project is to determine the basic mechanisms of glucose transport in rat vascular smooth muscle cells (VSMC) both in basal and hormone-stimulated states./ We hope to link cation- related effects of insulin and IGF-1 to these hormones' effects on VSMC glucose transport. Previous research indicates that glucose increases erythrocyte and adipocyte calcium levels, and if this is true in VSMC, a mechanism by which hyperglycemia and insulin resistance (both characteristic of type II diabetes mellitus) may contribute to the increased prevalence in hypertension in this diseased state may be ascertained. Pure populations of VSMC are required for these experiments since we wish to determine direct effects of hormones on these cells while avoiding endothelial- dependent mechanisms. Specific research aims include 1) determining insulin and IGF-1 concentrations necessary to stimulate glucose transport, 2) determining the hormone receptors required for such effects, 3) determining the specificity of hexoses transported into VSMC, 4) determining the direct effects of glucose loading on intracellular calcium dynamics and 5) determining if these hormonal events are altered in state of insulin resistance associated with hypertension (using the Zucker obese rat model for insulin resistance / hypertension). All proposed techniques are currently in use in the laboratories of the A1s. Specific student participation aims are as follows; Both students will learn VSMC isolation and tissue culture techniques. One student will concentrate on the hormonal modulation of glucose transport in these cells while another student will determine the effects of cellular glucose loading on intracellular calcium signalling. Both students will become expert in several techniques that 1) will aid them in their own project and 2) will afford them hands on training in other techniques that will increase the breadth of their knowledge in laboratory techniques in general. Students will be encouraged to work independently as soon s they feel comfortable and demonstrate their research process and will be involved in all aspects of data acquisition, manipulation and interpretation as well as abstract and manuscript preparation. Students will report their findings at weekly lab meetings and, if appropriate, at local and national scientific meetings. The health relevance is that the proposed research will increase our knowledge about smooth muscle abnormalities associated with several diseased states. Modulation of VSMC glucose transport and cellular calcium physiology have been implicated in hypertension, diabetes and atherosclerosis.
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