POSTSYNAPTIC ALPHA-1-BLOCKADE WITH TERAZOSIN DOES NOT MODIFY INSULIN SENSITIVITY IN NONOBESE NORMOTENSIVE SUBJECTS

Plasma insulin levels and the sensitivity of peripheral tissue to insulin (S(I)) have pathophysiological, therapeutic, and possibly also prognostic relevance. To investigate the effects of short-term selective alpha-1-adrenergic receptor blockade in nonobese normotensive humans on glucose and lipoprotein homeostasis, we assessed S(I) (determined by the minimal model method of Bergman), before and after glucose load plasma, glucose, and insulin levels, serum total triglycerides and lipoprotein cholesterol fractions, and some other variables in 20 healthy young men (26 +/- 1 years old, mean +/- SEM) during placebo and after 5 weeks of terazosin administration at a dose up to 10 mg once daily. Measurements were made after 3 days of standard diet (2,500 kcal/day, 45% carbohydrates, 40% fat, and 15% proteins) and after an overnight fast. Compared to placebo, terazosin decreased the upright systolic blood pressure (placebo vs. terazosin: 125 +/- 2 vs. 117 +/- 2 mm Hg, p < 0.05) and increased supine (63 +/- 2 vs. 70 +/- 1 beats/min, p < 0.05) and upright (77 +/- 2 vs. 88 +/- 2 beats/min, p < 0.01) heart rates, while the body weight was unaltered. Terazosin did not significantly modify fasting plasma glucose (5.08 +/- 0.09 vs. 5.23 +/- 0.08 mmol/L, respectively), or insulin (8.9 +/- 0.5 vs. 8.6 +/- 0.6-mu-U/ml), S(I) (14.3 +/- 1.8 vs. 11.8 +/- 1.5 x 10(-4)/min/mu-U/ml), the areas under the insulin or glucose curves, serum total triglycerides, and cholesterol or lipoprotein cholesterol fractions. These findings indicate that selective alpha-1-adrenergic receptor blockade with terazosin may not adversely affect insulin sensitivity and secretion as well as lipoprotein regulation in nonobese normotensive men.