ACUTE CHOLINERGIC BLOCKADE WITH LOW-DOSE PIRENZEPINE REDUCES THE INSULIN AND GLUCOSE RESPONSES TO A MIXED MEAL IN OBESE WOMEN WITH THE POLYCYSTIC-OVARY-SYNDROME

OBJECTIVES Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal i n a dose dependent fashion in normals and in patients with non-insulin dependent diabetes. We have studied the effects of pirenzepine on pla sma insulin, plasma glucose, growth hormone (GH), androstenedione, tes tosterone, insulin-like growth factor-I (IGF-I) and IGF binding protei n 1 (IGFBP-1) responses to a mixed meal in obese clinically hyperandro genic women with the polycystic ovary syndrome. SUBJECTS AND METHODS S ix obese women with polycystic ovary syndrome (BMI range 27.3-39.8 kg/ m(2)) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a sta ndard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours. RESUL TS Mean fasting plasma insulin concentrations were increased. Peak pos t-prandial plasma insulin concentrations were reduced significantly by all three doses used. Post-prandial integrated plasma insulin concent rations were reduced by the two higher doses. Peak postprandial plasma glucose concentrations were also reduced. The late post-prandial GH s urge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF-I and IGFBP-1 concentrations were n ot significantly different when placebo was compared with pirenzepine 200 mg. CONCLUSIONS Acute cholinergic muscarinic blockade with pirenze pine significantly reduces meal stimulated plasma insulin and plasma g lucose concentrations in clinically hyperandrogenic women with polycys tic ovary syndrome. The ability of pirenzepine to reduce plasma insuli n without worsening glycaemia is a particular advantage and may be the rapeutically relevant. Further studies are under way to assess the use fulness of pirenzepine in long-term suppression of plasma insulin in t his group of patients.