Introduction & Objectives: Our laboratory previously demonstrated a beneficial effect of amitriptyline, a serotonin and norepinephrine reuptake inhibitor, in preventing impaired hypoglycemic counterregulation. We wished to extend these findings to a diabetic animal model.
Methods: Streptozotocin (STZ, 65 mg/kg IP) diabetic 10-week-old male Sprague Dawley rats were randomized to 3 groups: STZ+RS (n=7, RS=recurrent saline controls), STZ+RH (n=6, RH=recurrent hypoglycemia), and STZ+AMP+RH (n=8, AMP=amitriptyline 10 mg/kg, IP). After 3-days preconditioning, animals underwent a hyperinsulinemic (50mU/kg/min) hypoglycemic (~45 mg/dL) clamp.
Results: In response to hypoglycemia, peak epinephrine levels were blunted in STZ+RH (299±51 pg/ml) compared to STZ+RS (1084±916, p<0.01 vs STZ+RS), and did not improve significantly in STZ+AMP+RH (482±227, p=NS vs STZ+RH). Similarly, the glucagon response to hypoglycemia demonstrated a blunted response with STZ+AMP+RH (see Figure).
Conclusion: The beneficial effects of amitriptyline in restoring the counterregulatory response to hypoglycemia that were initially observed in nondiabetic model seem to be attenuated in the insulin deficient diabetic rodent model. It is concluded that chronic diabetes abrogates the beneficial effects of serotonin and norepinephrine reuptake inhibitors on the sympathoadrenal and counterregulatory responses to hypoglycemia.
M.B. Music: None. A. Thompson: None. A. Iles: None. A.R. Marksbury: None. B. Patel: None. L.A. Schoeder: None. M. Wooten: None. Z. Beckner: None. M.H. Devore: None. E.L. Macon: None. S.J. Fisher: None.
