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2018 Abstracts

Treatment of Hypoglycemia Unawareness by Tricyclic Antidepressants

Parker Howe; Adriana Vieira De Abreu; Rahul Agrawal, University of Utah

In the treatment of diabetes, one of the most frequent complications is hypoglycemia (low blood glucose). People with long-standing Type 1 diabetes often develop a condition known as hypoglycemia unawareness, which involves the loss of warning symptoms of hypoglycemia that would normally prompt a corrective behavioral response, such as eating food. People with hypoglycemia unawareness are at 6-fold increased risk for severe, life-threatening hypoglycemia. With a goal of re-purposing FDA approved drugs for the treatment of hypoglycemia unawareness, we tested the hypothesis that tricyclic antidepressants (TCAs) would act in the brain to restore the awareness of hypoglycemia. Based on the fact that TCAs inhibit serotonin and norepinephrine reuptake in the brain and have anticholinergic effects, it was hypothesized that TCA mediated increases in serotonin and norepinephrine levels in the brain could potentially increase neuronal outflow and augment awareness of falling blood glucose levels. Thus, five groups of 8-10 week old, male, Sprague Dawley rats were studied. Hypoglycemia awareness was noted in these rats by measuring food intake in response to insulin-induced (NPH insulin, 15 units/kg; s.c.) hypoglycemia (35-40 mg/dl). We observed that when compared to saline injected control rats (CONT; n=15), insulin induced hypoglycemic rats (HYPO; n=12) increased their food intake three-fold (p