Nancy C. Tkacs, PhD

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				Nancy C. Tkacs, Ph.D. Associate Professor of Physiology in Nursing 128 Nursing Education Building 215-573-3045 (office) 215-573-4470 (lab email: tkacs@nursing.upenn.ed Click here for selected publications since Dr. Tkacs' arrival at Penn RESEARCH INTERESTS Neuroendocrine and autonomic responses to pathophysiological challenges; hypoglycemia-associated autonomic failure RESEARCH TECHNIQUES Physiological monitoring of chronically instrumented rodents, immunocytochemistry, in situ hybridization RESEARCH SUMMARY Intensive management of type 1 diabetes mellitus is associated with a high incidence of severe hypoglycemia. Recurrent severe hypoglycemia in insulin-treated individuals is associated with reduced ability to recognize and recover from hypoglycemia. Thus, these individuals fail to perceive deepening hypoglycemia (hypoglycemia unawareness) and demonstrate reduced responses of hormones like epinephrine that normally counteract the actions of insulin and restore normal blood glucose (hypoglycemia-associated autonomic failure). My lab is refining a rodent model of hypoglycemia-associated autonomic failure with the aim of identifying central nervous system loci of reduced responsiveness to hypoglycemia. After a single episode of severe hypoglycemia that did not result in coma or seizures, rats had reduced plasma epinephrine responses to a second bout of hypoglycemia 48 hours later. In addition, by 48 hours after severe hypoglycemia there was evidence of apoptosis and altered neuropeptide Y gene expression in neurons of the arcuate nucleus of the hypothalamus. The lab is presently refining this model and determining the time course of recovery of normal hormone responses to hypoglycemia after a single bout of antecedent hypoglycemia. In addition, mapping experiments are characterizing the arcuate and other brain regions responding to hypoglycemia and activating appropriate hormone responses. These regions will be studied using in situ hybridization to detect altered gene expression after antecedent hypoglycemia. The long term goal of these studies is to elucidate the nature of hypoglycemia-associated brain changes with the hope of reducing morbidity and mortality from hypoglycemia in insulin-treated diabetic patients. KEY WORDS: Hypoglycemia, autonomic, neuroendocrine, hypothalamus