CHOLINERGIC ENHANCEMENT BY PYRIDOSTIGMINE INCREASES THE INSULIN-RESPONSE TO GLUCOSE-LOAD IN OBESE PATIENTS BUT NOT IN NORMAL SUBJECTS

OBJECTIVES: To further investigate the role, a any, of acetylcholine a nd the parasympathetic nervous system in modulating beta-cell secretio n in man. DESIGN: Oral glucose load (OGTT, 100 g p.o. at 0 min) alone and preceded by pyridostigmine (PC, 120 mg p.o., 60 min before OGTT), a cholinesterase inhibitor, were administered on two different occasio ns, in random order, two or three days apart. SUBJECTS: Ten women with central obesity (OB, body mass index(BMI): 34.3 +/- 2.1 kg/m(2), wais t to hip ratio (WHR): 0.83 +/- 0.01, aged 39.0 +/- 5.3 y) and six norm al women (NS, BMI: 22.7 +/- 1.9 kg/m(2), WHR: 0.74 +/- 0.01, aged 37.1 +/- 4.8 y) were studied. MEASUREMENTS: Serum insulin, plasma glucose and plasma noradrenaline (NA) were measured at -60, -15 and 0 min, and then every 15 min up to +120 min. Insulin concentrations were measure d in duplicate by immunoradiometric assay, glucose by glucose oxidase colorimetric method and NA was assayed after extraction with alumina u sing high performance liquid chromatography with electrochemical detec tion. pulse rate (PR), systolic (SEP) and diastolic blood pressure (DB P) were also measured every 15 min during the tests by an automated cu ff device. RESULTS: OGTT raised glucose concentrations in OB and NS (i ncremental area: 420 +/- 44 vs 288 +/- 70 mmol/l. 2h, respectively) wi thout significant differences between groups(F = 0.6, P = ns). On the other hand, OB showed an insulin response to OGTT higher than NS (1012 0 +/- 1074 vs 6692 +/- 1962 mu U ml(-1) 2 h, respectively P < 0.01). A fter OGTT alone NA concentrations increased to the same extent in NS ( peak vs basal: 1.40 +/- 0.16 vs 1.07 +/- 0.10 nmol/l, P < 0.05) and in OB (peak vs basal: 1.50 +/- 0.14 vs 1.04 +/- 0.18 nmol/l P < 0.05). B oth in NS and in OB, PD administration failed to modify basal glucose and insulin (P = ns for both) as well as basal NA concentrations. In N S, the combined administration of PD and OGTT did not modify glucose a nd insulin responses compared to OGTT alone 335 +/- 65.4 mmol/l. 2 h a nd 6348 +/- 1384 mu U ml(-1) 2h, respectively) while in OB, PD signifi cantly increased the insulin response to OGTT (14640 +/- 3030 mu U ml( -1) 2 h, P < 0.03), while the glucose response was not significantly d ifferent from OGTT alone (478 +/- 45 mmol/l. 2h). PD administration di d not modify the NA response to OGTT, in NS or OB (P= ns). In both gro ups, pyridostigmine administration did not affect systolic or diastoli c brood pressures, but decreased pulse rate to the same extent in NS ( 74 +/- 2 vs 66 +/- 2 beats/min, P < 0.05) and in OB (72 +/- 1 vs 67 +/ - 2 beats/min, P < 0.05). CONCLUSIONS: Our present data indicate that in man, as in animals, acetylcholine has a stimulatory influence on in sulin secretion.