INSULIN SENSITIVITY AND ATRIAL-NATRIURETIC-FACTOR DURING BETA-RECEPTOR MODULATION WITH CELIPROLOL IN NORMAL SUBJECTS

beta-Receptor blockers may exert a spectrum of metabolic and humoral effects, which might differ depending on the specific adrenoreceptor characteristics of the individual agents. We investigated the influence of celiprolol, a beta(1)-blocker with beta(2)-agonistic and, possibly, additional weak alpha-receptor antagonistic properties, on insulin sensitivity (S-I), glucose homeostasis, and lipid profile in 20 young, healthy, normotensive individuals. S-I, fasting plasma glucose and insulin, serum total triglycerides (TG), lipoprotein cholesterol (C) fractions, lipoprotein a [Lp(a)], and plasma atrial natriuretic factor (ANF) levels were determined before and after acute glucose loading under placebo conditions and after 3 weeks of celiprolol administration. The participants were instructed to follow a 3-day standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% protein) and an overnight fast before measurements were recorded. As compared with control values, S-I, fasting plasma glucose and insulin, the areas under the glucose and insulin curves, the k value of glucose disappearance after glucose load, and serum cholesterol fractions, TG, and Lp(a) were unchanged during celiprolol administration. However, celiprolol significantly reduced plasma ANF levels (p < 0.02). The latter increased in response to acute hyperglycemia/hyperinsulinemia with placebo (p < 0.05) but not with celiprolol. Although diastolic blood pressure (DBP) decreased slightly during the first and second week of celiprolol administration, BP and heart rate (HR) did not differ significantly after 3 weeks on celiprolol treatment as compared with placebo conditions. Our findings demonstrate that in healthy lean humans beta-receptor modulation with celiprolol is neutral with regard to S-I and lipoprotein metabolism. Moreover, glucose loading stimulates whereas celiprolol decreases plasma ANF levels.