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 β 1-adrenoceptor antagonist and additional β 2-agonistic properties, administered by gavageeither 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 β 1-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 β 1-antagonist β 2-agonist celiprolol has a specific effect of improving insulin-stimulated skeletal muscle glucose transport that is independent of any hemodynamic alterations.
Published Version
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