Amitraz-induced glucose intolerance in rats: antagonism by yohimbine but not by prazosin.
Amitraz (N'-[2,4-dimethylphenyl]-N-[(2,4-dimethylphenyl)imino]-N- methylmethanimidamide) is a formamidine insecticide/acaricide that increases plasma glucose and decreases plasma insulin concentrations in dogs when applied topically. Because amitraz activates alpha 2-adrenoceptors in numerous tissues, in this study we used rats as a model to determine whether these effects of amitraz are mediated by alpha 2-adrenoceptors. The i.v. injection of amitraz (0.1, 0.3, and 1 mg/kg) followed by i.v. glucose injection (1 g/kg) induced a dose-dependent glucose intolerance characterized by hypoinsulinemia. At 1 mg/kg, amitraz completely blocked the insulin release induced by i.v. glucose administration. The alpha 2-adrenoceptor antagonist yohimbine (1 mg/kg, i.v.) prevented the effects of amitraz, but the alpha 1-adrenoceptor antagonist prazosin (0.3 mg/kg, i.v.) did not. The results suggested that one mechanism by which amitraz prolongs glucose-induced hyperglycemia is via inhibition of insulin release and this effect is mediated by alpha 2-adrenoceptors.
Smith
B E
BE
Department of Veterinary Physiology and Pharmacology, Iowa State University, Ames 50011.
Hsu
W H
WH
Yang
P C
PC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000633:toxicity*; D007328:Insulin / Q000097:blood; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology; D014052:Toluidines / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015016:Yohimbine / Q000494:pharmacology*
D001786:Blood Glucose; D007306:Insecticides; D007328:Insulin; D011941:Receptors, Adrenergic; D014052:Toluidines; D015016:Yohimbine; C014983:amitraz; D011224:Prazosin