Assistant Professor
Internal Medicine
Cell Biology and Physiology
Email Website Contact Info
Insulin resistance associated with Type 2 diabetes is also closely linked to two other major health problems, obesity and atherosclerosis. Since the basic defect underlying insulin resistance in Type 2 diabetes remains uncertain, our laboratory efforts to define the mechanism of insulin action will both increase understanding of this disease and also help in developing new, more effective therapeutic modalities. By defining the nature of metabolic cross-talk between insulin responsive tissues, our research strives to unravel the similarities that link diabetes with closely associated disorders, such as the metabolic syndrome and obesity. Our findings suggest that impaired insulin action at target tissues not classically considered insulin sensitive, such as the brain, may contribute to the pathologic metabolism characteristic of diabetes and obesity.
The goals of our laboratory are; 1) to understand how hormones (i.e., insulin and leptin) and nutrients (i.e., glucose and fatty acids) act in the central nervous system to alter signal transduction, neuropeptide expression, and brain nutrient utilization; 2) to understand the mechanism by which these alterations in the central nervous system mediators (especially in the hypothalamus) regulate metabolism in key peripheral tissue (i.e., muscle, fat, liver) in the pathogenesis and potential treatment of diabetes and obesity; and 3) to characterize the mechanism by which insulin acts to modulate hypothalamic glucose sensors and increase the stress response to hypoglycemia (low blood sugar). To pursue these goals, our laboratory utilizes techniques of molecular biology, physiology, biochemistry, pharmacology, neuroscience, and genetics with the in vivo characterization of transgenic and tissue specific knockout models.
Research Publications
Fisher SJ, Bruning JC, Lannon S, Kahn CR (2005 May). Insulin signaling in the central nervous system is critical for the normal sympathoadrenal response to hypoglycemia. Diabetes. 54 (5): 1447-51. Full Article >
Jimenez-Chillaron JC, Hernandez-Valencia M, Reamer C, Fisher S, Joszi A, Hirshman M, Oge A, Walrond S, Przybyla R, Boozer C, Goodyear LJ, Patti ME (2005 Mar). Beta-cell secretory dysfunction in the pathogenesis of low birth weight-associated diabetes: a murine model. Diabetes. 54 (3): 702-11. Full Article >
Chen D, Mauvais-Jarvis F, Bluher M, Fisher SJ, Jozsi A, Goodyear LJ, Ueki K, Kahn CR (2004 Jan). p50alpha/p55alpha phosphoinositide 3-kinase knockout mice exhibit enhanced insulin sensitivity. Mol Cell Biol. 24 (1): 320-9. Full Article >
Fisher SJ, Kahn CR (2003 Feb). Insulin signaling is required for insulin's direct and indirect action on hepatic glucose production. J Clin Invest. 111 (4): 463-8. Full Article >
Norris AW, Chen L, Fisher SJ, Szanto I, Ristow M, Jozsi AC, Hirshman MF, Rosen ED, Goodyear LJ, Gonzalez FJ, Spiegelman BM, Kahn CR (2003 Aug). Muscle-specific PPARgamma-deficient mice develop increased adiposity and insulin resistance but respond to thiazolidinediones. J Clin Invest. 112 (4): 608-18. Full Article >
Contact Info
Simon Fisher, M.D., Ph.D.
Office Location: 832 Southwest Tower
Office Phone: 314-362-3268
Lab Phone: 314-362-7644
Campus Box: 8126
Fax: 314-362-7641
sfisher@im.wustl.edu
http://endo.wustl.edu/faculty/fisher.html
