Introduction & Objective: To investigate the potential of metoclopramide, a dopamine antagonist, in mitigating 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 (STZ+RS, n=6), 2) diabetic rats preconditioned with recurrent hypoglycemia (STZ+RH, n=7), and 3) diabetic rats preconditioned with recurrent hypoglycemia and metoclopramide (STZ+RH+MET: 3mg/kg IP, n=7). Following 3 days of preconditioning, all animals underwent a hyperinsulinemic (50mU/kg/min) hypoglycemic (~45 mg/dl) clamp.

Results: Glucose infusion rates to maintain hypoglycemia for STZ+RS (19±0.8 mg/kg/min) were higher in STZ+RH (27±0.9 mg/kg/min, p<0.0001 vs STZ+RS) and then reduced in STZ+RH+MET (24±0.1 mg/kg/min, p<0.05 vs STZ+RH). The glucagon response to hypoglycemia in control STZ+RS (p<0.05 vs basal) was abrogated in STZ+RH (p=NS vs basal) and restored in STZ+RH+MET (p<0.05 vs basal).

Conclusions: In this model of insulin deficient diabetes, the detrimental effect of recurrent hypoglycemia on glucoregulatory and counterregulatory hormonal response to hypoglycemia was reversed with metoclopramide treatment. It is concluded that the impaired response to hypoglycemia may be regulated via dopaminergic signaling.

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Disclosure

M.H. Devore: None. A. Iles: None. L.A. Schoeder: None. M.B. Music: None. B. Patel: None. A.R. Marksbury: None. M. Wooten: None. A. Thompson: None. Z. Beckner: None. E.L. Macon: None. S.J. Fisher: None.

Funding

R01DK1180825T32DK0913171R25DK1098941T32DK110966

© 2024 by the American Diabetes Association
2024
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