Introduction and Objective: To investigate the potential of metoclopramide, a dopamine antagonist, in restoring impaired hypoglycemic counterregulation in a diabetic animal model.Methods: Diabetes was induced in 10-week-old Sprague-Dawley rats with streptozotocin (STZ, 65 mg/kg IP). Rats were randomized into three groups: 1) diabetic controls treated with recurrent saline (DRS, n=6), 2) diabetic rats preconditioned with recurrent hypoglycemia (DRH, n=4), and 3) diabetic rats preconditioned with recurrent hypoglycemia and metoclopramide (STZ+RH+MET: 3mg/kg IP, n=5). Following preconditioning protocols, all animals underwent a hyperinsulinemic (200mU/kg/min) hypoglycemic (~45 mg/dl) clamp.Results: Epinephrine response to hypoglycemia in DRS (3000 ± 1060 pg/mL) was blunted in DRH (1210 ± 358 pg/mL) and was restored with metoclopramide treatment (DRHM: 3420 ± 779 pg/mL).Conclusion: In this model of insulin deficient diabetes, the detrimental effect of recurrent hypoglycemia on the counterregulatory hormonal response to hypoglycemia was restored with metoclopramide treatment. These results indicate a role for dopaminergic pathways in the treatment of impaired hypoglycemic counterregulation.
M. Devore: None. R. Zohary: None. E.W. Brockman: None. Z. Beckner: None. L. Schoeder: None. J. Zohary: None. W.H. Hall: None. S. Fisher: None.
Bill Gatton Foundation Fellowship and TL1TR001997 to MD.R01DK118082 to SJF.
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