164-OR: Metoclopramide Restores the Counterregulatory Response to Hypoglycemia in Rodents

Abstract

To test the hypothesis that metoclopramide (a dopamine antagonist) may restore hypoglycemic counterregulation, 10-week old rats underwent recurrent (insulin-induced) hypoglycemia (RH) to induce a blunted sympathoadrenal response. RH rats were treated with vehicle or metoclopramide (RH+MET: 3 mg/kg IP) . A third control group did not undergo recurrent hypoglycemia (RS: recurrent saline) . MET was administered either during RH phase (concurrent protocol) or after RH (post-induction protocol) . All rats (n=7-14/group) underwent a hyperinsulinemic (50mU/kg/min) hypoglycemic (45±5 mg/dl) clamp. In the concurrent protocol, epinephrine response to hypoglycemia in RS (1434±275 pg/ml) was blunted in RH (460±1pg/ml, p<0.vs. RS) and increased with MET (1072±141 pg/ml, p<0.vs. RH) . In the post-induction protocol, epinephrine in RS (1949±413 pg/ml) was again blunted in RH (581±199 pg/ml, p<0.vs. RS) and increased with MET (1460±202 pg/ml, P<0.vs. RH) . In summary, 1) metoclopramide prevented the development of an impaired sympathoadrenal response to hypoglycemia, and 2) in rodents that had an impaired response to hypoglycemia, subsequent metoclopramide treatment restored the sympathoadrenal response. In conclusion, 1) dopaminergic signaling plays a role in the development of impaired counterregulation, and 2) post hoc treatment with metoclopramide improves the sympathoadrenal response to hypoglycemia. Disclosure M.H.Devore: None. S.Sharma: None. S.Fisher: None. Funding NIH R01DK118082