Abstract
Parasympathetic nervous system is known to affect insulin secretion in animal and man and there is evidence that it is involved in the outcome of spontaneous and stimulated insulin hypersecretion observed in animal obesity. In human obesity, there are contradictory data. We studied the effect of 150 mg orally administered pirenzepine (PNZ), a muscarinic 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 18 obese subjects normotolerant to glucose. PNZ did not modify basal serum insulin and the hormone response to either intravenous glucose (AUC: 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 vs 8614.3±1095.2 mU/L-min). Actually, the insulin rises at +30 min after 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 ANCOVA 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 that acetylcholine positively influences insulin secretion in humans, likely via indirect mechanisms.
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Bergman R.N., Miller R.E. Direct enhancement of insulin secretion by vagal stimulation of the isolated pancreas. Am. J. Physiol. 225: 481, 1973.
Bloom S.R., Edwards A.V. Pancreatic endocrine responses to stimulation of peripheral ends of the vagus nerves in conscious calves J. Physiol. 315: 31, 1981.
Ahren B., Taborsky Jr. G.J. The mechanism of vagal nerve stimulation of glucagon and insulin secretion in the dog. Endocrinology 118: 1551, 1986.
Iversen J. Effect of acetylcholine on the secretion of glucagon and insulin from the isolated, perfused canine pancreas. Diabetes 22: 381, 1973.
Kaneto A., Kajinuma H., Kosaka K., Nakao K. Stimulation of insulin secretion by parasympathomimetic agents. Endocrinology 83: 651, 1968.
Chen N.-G., Romsos D.R. Enhanced sensitivity of pancreatic islets from preobese 2-week old ob/ob mice to neurohormonal stimulation of insulin secretion. Endocrinology 136: 505, 1995.
Strubbe J.H. Parasympathetic involvement in rapid meal-associated conditioned insulin secretion in the rat. Am. J. Physiol. 263: R615, 1989.
Larrimer J.N., Mazzaferri E.L., Cataland S., Mekhjian H.S. Effect of atropine on glucose-stimulated gastric inhibitory polypeptide. Diabetes 27: 638, 1978.
Jeanrenaud B., Halimi S., Van de Werve G. Neuro-endocrine disorders seen as triggers of the triad: obesity-insulin resistance-abnormal glucose tolerance. Diabetes Metab. Rev. 1: 261, 1985.
Lee H.C., Curry D.L., Stern J.S. Direct effect of CNS on insulin secretion in obese zucker rats: involvement of vagus nerve. Am. J. Physiol. 256: E439, 1989.
Rohner-Jeanrenaud F., Jeanrenaud B. Involvement of the cholinergic system in insulin and glucagon oversecretion of genetic preobesity. Endocrinology 116: 834, 1985.
Tappy L., Chiolero R., Randin J.P., Burckhardt P., Felber J.P. Effects of cholinergic stimulation and antagonism on plasma insulin concentration in lean and obese humans subjects. Horm. Metab. Res. 18: 821, 1986.
Schneeberger D., Tappy L., Temler E., Jequier E. Effects of muscarinic blockade on insulin secretion and on glucose-induced thermogenesis in lean and obese human subjects. Eur. J. Clin. Invest. 21: 608, 1991.
El-Sabbagh H.N., Bloom S.R., Adrian T.E., Prinz R.A., Baron J.H., Welbourn R.B. The effect of pirenzepine on meal-stimulated gastrointestinal hormones. Scand. J. Gastroenterol. 15: 57, 1980.
Coiro V., Chiodera P., Volpi R., D’Amato L., Camellini L., Rossi G., Pignatti D., Butturini U. Muscarinic cholinergic modulation of insulin response to an intravenous glucose tolerance test in normal man. J. Endocrinol. Invest. 9: 27, 1986.
Page M.D., Bevan J.S., Dieguez C., Peters J.R., Scanion M.F. Cholinergic blockade with pirenzepine improves carbohydrate tolerance and abolishes the GH response to meals in normal subjects. Clin. Endocrinol. (Oxf.) 30: 519, 1989.
Bevan J.S., Ara J., Page M.D., Scanion M.F., Peters J.R. Cholinergic blockade with pirenzepine induces dose-related reduction in glucose and insulin responses to a mixed meal in normal subjects and non-insulin dependent diabetics. Clin. Endocrinol. (Oxf.) 35: 85, 1991.
Premawardhana L.D.K.E., Ismail I.S., Riad-Fahmy D., Miel J.P., Peters J.R., Scanlon M.F. Acute cholinergic blockade with low dose of pirenzepine reduces the insulin and the glucose responses to a mixed meal in obese women with the polycystic ovary sindrome. Clin. Endocrinol. (Oxf.) 40: 617, 1994.
Le Marchand Y., Freychet P., Jeanrenaud B. Longitudinal study on the establishment of insulin resistance in hypothalamic obese mice. Endocrinology 102: 74, 1978.
Delitala G., Frulio T., Pacifico A., Maioli M. Participation of cholinergic muscarinic receptors in glucagon and arginine mediated growth hormone secretion in man. J. Clin. Endocrinol. Metab. 55: 1231, 1982
Cooke A.R., Clark E.D. Effect of first part of duodenum on gastric emptying in dogs: response to acid, fat, glucose, and neural blockade. Gastroenterology 70: 550, 1976.
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Maccario, M., Grottoli, S., Procopio, M. et al. Effects of cholinergic blockade by pirenzepine on insulin and glucose response to oral and intravenous glucose and to arginine load in obesity. J Endocrinol Invest 20, 8–12 (1997). https://doi.org/10.1007/BF03347965
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DOI: https://doi.org/10.1007/BF03347965