RESEARCH--The glucose transport proteins of rodent glomerular cells will be identified and characterized by the use of nucleic acid and antibody probes from cloned glucose transporters. This will permit the study of their localization, relative abundance, and regulation by various factors which may pertain to disease states such as diabetic nephropathy. The brain/erythrocyte and insulin-responsive glucose transporter (GT) mRNAs have been detected in rat and mouse cultured mesangial cells. Further specific aims of the project include: 1) Identification of other GT mRNAs present in whole glomerulus and glomerular cells. 2) Detection of the various GT proteins in these tissues by specific antibodies to the cloned GTs. 3) The cloning and sequencing of cDNAs corresponding to novel GT mRNAs in these tissues.. 4) Determination of the level of GT mRNA and protein expression in glomeruli from diabetic rats before and after insulin therapy and in glomeruli from fasting rats. 5) Determination of the levels of GT expression in glomerular cells grown in media containing variable glucose, insulin and other growth factor concentrations. 6) Transfection of mesangial cells and glomerular epithelial cells with vectors containing the various GT cDNAs in order to determine the effect of novel expression or over-or underexpression of GTs on glomerular cell growth and morphology. 7) Correlation of the changes in GT expression to changes in expression of other proteins expressed by glomerular cells. 8) Use of co-culture systems allowing two or more of the glomerular cell types to be grown in proximity and determination of the effects of such co-culture on GT expression. ENVIRONMENT--The University of Michigan with its kidney center for the study of glomerular disease, and its close ties to the Department of Pathology, other basic science departments and the Howard Hughes Institute will provide an ideal environment for this research. Dr. Wiggins and the other sponsors will be able to provide specialized guidance in those fields as yet unfamiliar to the candidate.
| Heilig, C W; Liu, Y; England, R L et al. (1997) D-glucose stimulates mesangial cell GLUT1 expression and basal and IGF-I-sensitive glucose uptake in rat mesangial cells: implications for diabetic nephropathy. Diabetes 46:1030-9 |
| Brosius 3rd, F C; Nguyen, K; Stuart-Tilley, A K et al. (1995) Regional and segmental localization of AE2 anion exchanger mRNA and protein in rat kidney. Am J Physiol 269:F461-8 |
| Marcus, R G; England, R; Nguyen, K et al. (1994) Altered renal expression of the insulin-responsive glucose transporter GLUT4 in experimental diabetes mellitus. Am J Physiol 267:F816-24 |
| Brosius 3rd, F C; Briggs, J P; Marcus, R G et al. (1992) Insulin-responsive glucose transporter expression in renal microvessels and glomeruli. Kidney Int 42:1086-92 |
