Frank C. Brosius, M.D.  ~Professor of Internal Medicine Interim Divisional Chief ~Professor of Molecular & Integrative Physiology M.D.: University of Kansas  Residency: University of Michigan Fellowships: Beth Israel Hospital (Boston, MA)  Whitehead Institute for Biomedical Research, Cambridge, MA  1150 W. Medical Center Dr  1560 MSRB II Ann Arbor, MI 48109-0676  734)764-3157 fbrosius@umich.edu

Current Research: 

Pathways by which glucose transporter expression affects cell death and the pathogenesis of diabetic nephropathy; abnormalities of glucose transport and metabolism in the pathogenesis of vascular changes in hypertension.

We have found that the GLUT1 glucose transporter reduces hypoxia-induced apoptosis in cardiac myocytes and vascular smooth muscle cells. This protection appears to be due in part to GLUT1-induced reduction in levels or activity of Hif-1a, p53, GSK-3, and JNK as well as induction of Akt activity. On the other hand, glucose transporter expression appear to promote the development of diabetic kidney disease. Overexpression of GLUT1 increases extracellular matrix protein accumulation. Pathways by which changes in GLUT1 lead to nephropathy are being explored. Diabetes and high glucose also is toxic to glomerular podocytes and leads to podocyte loss. As part of a NIH consortium, we are developing novel mouse models of diabetic nephropathy that recapitulate these abnormalities. We are now studying how glucose transport contributes to vascular smooth contractility and morphologic changes in hypertension. Finally, with Drs. David Smith and Richard Keep, we have developed a mouse model in which PepT2, a proton-coupled oligopeptide transporter, is knocked out and are exploring the phenotypes in kidney, brain and other organs.

Representative Publications:

Publications Heilig CW, Kreisberg JI, Freytag S, Murakami T, Ebina Y, Guo L, Heilig K, Jin Y, Loberg R, Henry D, Brosius FC III. Antisense-GLUT1 protects mesangial cells from D-glucose-induced transporter and fibronectin expression, Am J Physiol, 2001; 280:F657-666.

Atkins, KB, Johns D, Watts S, Webb RC, Brosius FC III. Decreased vascular glucose transporter expression and glucose uptake in DOCA-salt hypertension, J Hypertens 2001; 19:1581-1587.

Malhotra R, Lin Z, Vincenz C, Brosius FC III. Hypoxia-induced apoptosis in Jurkat cells progresses through two independent pathways differentially regulated by glucose uptake, Am J Physiol (Cell), 2001; 281:C1596-1603..

Malhotra R, Tyson D, Kumagi AK, Brosius FC III. Glucose uptake and adenoviral mediated GLUT-1 infection HIF-1a levels and decreases hypoxia-induced apoptosis in cardiac myocytes, J Mol Cell Cardiol 2002; 34:1063-1073.

Loberg RD, Vesely E, Brosius FC III. Enhanced glycogen synthase kinase-3b activity mediates hypoxia-induced apoptosis of vascular smooth muscle cells and is prevented by glucose transport and metabolism, J Biol Chem 2002; 277:41667-41673.

Shen H, Smith DE,. Keep RF, Xiang J, Brosius FC III. Targeted Disruption of the PEPT2 Gene Markedly Reduces Dipeptide Uptake in Choroid Plexus, J Biol Chem 2003;278:4786-91.

Park JL, Loberg RD, Deo BK, Coyle J, Kumagai AK, Brosius FC III. Glucose Uptake via GLUT4 Enhances Vascular Smooth Muscle Contraction in Mouse Aorta, submitted

Atkins KB, Northcott C, Watts S, Brosius FC III. Effect of thiazolidinediones on vascular smooth muscle markers in DOCA-salt hypertension, submitted

Back to list of faculty