title: Doxazosin lowers blood pressure and improves insulin responses to a glucose load with no changes in tyrosine kinase activity or insulin binding.
abstract: alpha-Adrenergic blockers have shown favorable metabolic effects. We evaluated the glucose and insulin responses to a glucose load and lipid profiles in 36 diabetic hypertensive patients before and after 8 weeks of doxazosin administration. To evaluate insulin action at the cellular level, erythrocyte insulin binding and tyrosine kinase (TK) activity were measured in 12 of these patients. Systolic and diastolic blood pressures decreased significantly (P < .0001) after 8 weeks of doxazosin therapy. Doxazosin administration significantly reduced the integrated insulin response (area under the curve [AUC]-insulin: 6093 +/- 894 to 5260 +/- 807; P = .04) and the insulin/glucose index (I/G) at 90 and 120 min after a glucose load (at 90 min, 0.230 +/- 0.055 v 0.180 +/- 0.04, P < .05; at 120 min, 0.275 +/- 0.071 v 0.173 +/- 0.036, P < .05). HDL3 level increased from 31.1 +/- 1.5 mg% to 34 +/- 1.6 mg% (P < .05) after doxazosin. Erythrocyte insulin binding and tyrosine kinase activity were not significantly altered after doxazosin. No significant correlation was found between the insulin or glucose responses and the insulin receptor binding or tyrosine kinase activity before and after treatment.
authors.affiliation: Division of Endocrinology, Wayne State University, Detroit, Michigan 48201, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Dominguez
authors.forename: M H
authors.initials: MH
authors.lastname: Weinberger
authors.forename: W T
authors.initials: WT
authors.lastname: Cefalu
authors.forename: D B
authors.initials: DB
authors.lastname: Jacobs
authors.forename: M
authors.initials: M
authors.lastname: Barbagallo
authors.forename: M F
authors.initials: MF
authors.lastname: Walsh
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017292:Doxazosin / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011505:Protein-Tyrosine Kinases / Q000097:blood* / Q000187:drug effects; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D017292:Doxazosin