title: The beta2-adrenergic modulator celiprolol reduces insulin resistance in obese Zucker rats.
abstract: Essential hypertension is associated with an increased incidence of insulin resistance of skeletal muscle glucose transport. The present study determined if celiprolol, an antihypertensive agent with selective beta1-adrenoceptor antagonist and additional beta2-agonistic properties, administered by gavage either acutely (3 hr) or chronically (14 d), had a direct effect on improving glucose tolerance and insulin-stimulated glucose transport activity (using 2-deoxyglucose (2-DG) uptake) in isolated epitrochlearis muscles of the insulin-resistant obese Zucker rat. The effects of a selective beta1-blocker, metoprolol, were also assessed. Acute administration of celiprolol, but not metoprolol, increased insulin-stimulated 2-DG uptake in muscle by 22% (p<0.05). Chronic celiprolol treatment significantly lowered fasting plasma insulin (22%) and free fatty acids (40%) in comparison to obese control values. Moreover, chronic celiprolol administration decreased the glucose-insulin index (calculated as the product of the glucose and insulin areas under the curve during an oral glucose tolerance test), by 32% (p<0.05) compared to obese controls, indicating that peripheral insulin action was increased. Indeed, insulin-stimulated skeletal muscle 2-DG uptake was enhanced by 49% (p<0.05) in these celiprolol-treated obese animals. Metoprolol was without significant effect on any of these variables following chronic administration. These findings indicate that, in this animal model of insulin resistance, the beta1-antagonist/beta2-agonist celiprolol has a specific effect of improving insulin-stimulated skeletal muscle glucose transport that is independent of any hemodynamic alterations.
authors.affiliation: Department of Endocrinology, Eberhard-Karls University, Tübingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Jacob
authors.forename: D L
authors.initials: DL
authors.lastname: Fogt
authors.forename: G J
authors.initials: GJ
authors.lastname: Dietze
authors.forename: E J
authors.initials: EJ
authors.lastname: Henriksen
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D017272:Celiprolol / Q000008:administration & dosage / Q000494:pharmacology*; D003847:Deoxyglucose / Q000378:metabolism; D005260:Female; D006973:Hypertension / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008790:Metoprolol / Q000008:administration & dosage / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D001786:Blood Glucose; D007328:Insulin; D003847:Deoxyglucose; D017272:Celiprolol; D008790:Metoprolol