Xylazine-induced Hyperglycemia in Cattle: A Possible Involvement of a2-Adrenergic Receptors Regulating Insulin Release

The mechanism by which xylazine raises plasma glucose but lowers insulin concentrations was examined in Holstein cows. Intravenous injection of xylazine (15-150 micrograms/kg) induced a dose-dependent hyperglycemia and hypoinsulinemia for 3-4 h. An alpha 2-adrenergic blocking agent, yohimbine, and an alpha 1- and alpha 2-adrenergic blocking agent, phentolamine, at 500 micrograms/kg each reduced or abolished xylazine-induced hyperglycemia and hypoinsulinemia. The alpha 1-adrenergic blocking agents, prazosin and phenoxybenzamine, at 500 micrograms/kg each did not exert such antagonism. Prazosin at the dose studied even prolonged xylazine-induced hypoinsulinemia. The alpha-adrenergic blocking agents alone at 500 micrograms/kg each did not change either plasma glucose or insulin concentrations. The present study suggests that xylazine-induced hyperglycemia and hypoinsulinemia are mediated by alpha 2-adrenergic receptors, possibly in beta-cells of pancreatic islets which inhibit the release of insulin. The present study further suggests the use of xylazine as a pharmacological tool in the study of adrenergic influence on in vivo insulin release.