Research Abstract:
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.
Selected Publications:
Bree A, Puente E, Daphna-Iken D, Fisher SJ. Diabetes worsens brain damage following insulin induced severe hypoglycemia. Am.J.Physiol. Endocrinol. Metab 297(1):E194-201, 2009.
Ishihara KK, Haywood SC, Daphna-Iken D, Puente E, Fisher SJ. Intrahypothalamic insulin does not augment the counterregulatory response to hypoglycemia or glucoprivation. Metabolism 58(6):812-20, 2009.
Haywood SC, Bree AJ, Puente EC, Daphna-Iken D, Fisher SJ. Central but not systemic lipid infusion lipid augments the counterregulatory response to hypoglycemia. Am.J.Physiol. Endocrinol. Metab. 297(1):E50-6 2009.
Fisher SJ, Brüning JC, Lannon S, Kahn CR. Insulin signaling in central nervous system is critical for the normal sympathoadrenal response to hypoglycemia. Diabetes 2005 54:1447-1451.
Fisher SJ, Kahn CR. Insulin signaling is required for insulin’s direct and indirect action on hepatic glucose production. J Clin Invest 2003 111:463-468.
Last Updated: 08/27/2009 |