EFFECTS OF CHOLINERGIC BLOCKADE BY PIRENZEPINE ON INSULIN AND GLUCOSERESPONSE TO ORAL AND INTRAVENOUS GLUCOSE AND TO ARGININE LOAD IN OBESITY

Parasympathetic nervous system is known to affect insulin secretion in animal and man and there is evidence that it is involved in the outco me of spontaneous and stimulated insulin hypersecretion observed in an imal obesity, In human obesity, there are contradictory data. We studi ed the effect of 150 mg orally administered pirenzepine (PNZ), a musca rinic receptor antagonist, on the insulin response to glucose (75 g po or 0.33 g/kg i.b.w. iv) or arginine (0.5 g/kg infused in 30 min) in 1 8 obese subjects normotolerant to glucose. PNZ did not modify basal se rum insulin and the hormone response to either intravenous glucose (AU G: 5221.6+/-1177.6 vs 5309.8+/-1534.8 mU/L min) or arginine load (4257 .9+/-832.7 vs 3952.8+/-549.3 mU/L min), Calculated as AUC the insulin response to oral glucose load was unaffected by PNZ (6601.5+/-1218.6 v s 8614.3+/-1095/2 mU/L min). Actually, the insulin rises at +30 min af ter oral glucose load was significantly blunted by PNZ (37.0+/-3.4 vs 81.6+/-16.9 mU/L; p<0.03). However, after statistical evaluation by AN COVA assuming basal insulin and +30 min glucose levels as covariates, this significance disappeared, Our present data do not agree with the hypothesis that the cholinergic system plays a role in the exaggerated insulin secretion of obesity, Nevertheless, these findings confirm th at acetylcholine positively influences insulin secretion in humans, li kely via indirect mechanisms. (C) 1997, Editrice Kurtis.