Interactions of doxazosin with insulin or glucagon in the ob/ob mouse.
Doxazosin, a selective inhibitor of alpha 1-adrenergic receptors, when administered alone or in combination with insulin or glucagon to mature ob/ob mice, consistently lowered levels of triglycerides, cholesterol, glycerol, and lactate and increased levels of beta-hydroxybutyrate and glucose. Doxazosin suppressed the tendency of insulin to elevate triglycerides but had no effect on the hypoglycemic response to insulin. Doxazosin and insulin together (but neither alone) lowered free fatty acids (FFA). Glucagon lowered cholesterol and raised glucose but did not affect triglycerides or beta-hydroxybutyrate. Analysis of variance indicates that a simple additive-effects model cannot explain the interactions between doxazosin and insulin on triglycerides, glucose, and FFA. It is suggested that the alpha 1-adrenergic system may contribute to glycemic control and to ambient hypercholesterolemia, especially in the presence of insulin resistance, as in ob/ob mice, and that the hypolipidemic response to alpha 1-adrenergic inhibition may involve insulin pathways.
Swindell
A C
AC
Central Research Division, Pfizer Inc., Groton, Connecticut 06340.
Valentine
J J
JJ
D020155:3-Hydroxybutyric Acid; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002784:Cholesterol / Q000097:blood; D017292:Doxazosin; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000494:pharmacology*; D005990:Glycerol / Q000097:blood; D006885:Hydroxybutyrates / Q000097:blood; D007328:Insulin / Q000494:pharmacology*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D011224:Prazosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D005230:Fatty Acids, Nonesterified; D006885:Hydroxybutyrates; D007328:Insulin; D007773:Lactates; D014280:Triglycerides; D019344:Lactic Acid; D005934:Glucagon; D002784:Cholesterol; D017292:Doxazosin; D005990:Glycerol; D020155:3-Hydroxybutyric Acid; D011224:Prazosin