Abstract
The effect of pirenzepine, a specific muscarinic cholinergic receptor antagonist, on insulin and glucagon responses to an intravenous injection of glucose was investigated in eight normal adult subjects. These volunteers received two iv glucose tolerance tests (0.33 g/kg) before and after the oral administration of 125 mg of pirenzepine (three doses of 25 mg during the day before the experiment and a fourth dose of 50 mg 2 h before glucose injection). Treatment with pirenzepine neither altered basal blood glucose levels nor affected glucose tolerance after the injection of the glucose load. In addition, it did not modify basal plasma insulin and glucagon levels and the decrement of glucagon in response to glucose injection. In contrast, pirenzepine significantly decreased insulin release induced by glucose administration. In man, during the present experimental conditions, the muscarinic cholinergic system modulates insulin, but not glucagon response to an iv glucose injection.
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Gerich J.E., Lorenzi M. The role of the autonomic nervous system and somatostatin in the control of insulin and glucagon secretion. In: Ganong W.F., Martini L. (Eds.), Frontiers in neuroendocrinology. Raven Press, New York, 1978, vol. 5, p. 265.
Honey R.N., Weir G.C. Acetylcholine stimulates insulin, glucagon, and somatostatin release in the perfused chicken pancreas. Endocrinology 107: 1065, 1980.
Iversen J., Denmark A. Effect of acetyl choline on the secretion of glucagon and insulin from the isolated, perfused canine pancreas. Diabetes 22: 381, 1973.
Lundquist I. Cholinergic muscarinic effects on insulin release in mice. Pharmacology 25: 338, 1982.
Malaisse W., Malaisse-Lagae F., Wright P.H., Ashmore J. Effects of adrenergic and cholinergic agents upon insulin secretion in vitro. Endocrinology 107: 924, 1980.
Malaisse W. Endocrine pancreas In. Steiner D.F, Frenkel N. (Eds.), Handbook of physiology. Williams and Wilkins, Baltimore, 1972, vol. 1, p. 237.
Wollheim C.B., Siegel E.G., Sharp G.W.G. Dependency of acetylcholine-induced insulin release on Ca++ uptake by rat pancreatic islets. Endocrinology 107: 924, 1980.
Woods S.C., Porte D. Jr. Neural control of the endocrine pancreas. Physiol. Rev. 54: 596, 1974.
Grill V., Ostenson C.G. Muscarinic receptors in pancreatic islets of the rat. Biochim. Biophys. Acta 756: 159, 1983.
Brown D.A., Forward A., March J. Antagonist discrimination between ganglionic and ileal muscarinic receptors. Br. J. Pharmacol. 71: 362, 1980.
Hammer R. Muscarinic receptors in the stomach. Scand. J. Gastroenterol. 15(Suppl. 66):. 5, 1980.
Hammer R., Berrie C.P., Birdsall N.J.M., Burgen A.S.V., Hulme E.C. Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature 223: 90, 1980.
Hammer R., Giachetti A. Muscarinic receptor subtypes: M1 and M2 biochemical and functional characterization. Life Sci. 31: 2991, 1982.
Watson M., Roeske W.R., Yamamura H.I. [H3] Pirenzepine selectively identifies a high affinity population of muscarinic cholinergic receptors in the rat cerebral cortex. Life Sci. 31: 2019, 1982.
Yamamura H.I., Watson M., Roeske W.R. [H3] Pirenzepine specifically labels a high affinity muscarinic receptor in the rat cerebral cortex. In: Mandel P., De Fendis F.V. (Eds.), Central nervous system receptors: from molecular pharmacology to behavior. Raven Press, New York, 1983, p. 331.
Conard V. L’épreuve d’hyperglycémie provoquée par voie intraveineuse. Acta Diabetol. Lat. 2: 447, 1965.
Unger R.H., Dobbs R.E., Orci L. Insulin, glucagon and somatostatin secretion in the regulation of metabolism. Annu. Rev. Physiol. 40: 307, 1978.
Bloom R.S., Edwards A.V. The role of the parasympathetic system the in control of insulin release. Diabetologia 19: 258, 1980.
Hakanson R., Liedberg G., Lundquist I. Effect of vagal denervation on insulin release after oral and intravenous glucose. Experientia 27: 460, 1971.
Heller G.M., Neubauer M., Althoff P., Kam U., Schöffling K. Pirenzepine: investigation of its mode of action in man. Proceeding of VI World Congress of Gastroenterology Madrid 5–9 June 1978, p. 213.
Stockbrügger R.B., Jaup B., Dotevall G.D. Pirenzepine a new antisecretory drug. Scand. J. Gastroenterol. 12(Suppl. 45): 103, 1977.
Bucolo R.J., Corvallis P.D. Obesity, hyperinsulinemia, and portal blood flow. A theoretic study of the effects of increased portal blood flow upon fasting peripheral insulin concentrations. Diabetes 27: 840, 1978.
Ahrén B., Lundquist I. Effect of autonomic blockade by methylatropine and optical isomers of propanolol on plasma insulin levels in the basal state and after stimulation. Acta Physiol. Scand. 112: 57, 1981.
Frohman L.A., Ezdinli E.Z., Javid R. Effect of vagotomy and vagal stimulation on insulin secretion. Diabetes 16: 443, 1967.
Coupland R.E. The innervation of pancreas of the rat, cat and rabbit as revealed by the cholinesterase technique. J. Anat. 92: 143, 1958.
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Coiro, V., Chiodera, P., Volpi, R. et al. Muscarinic cholinergic modulation of insulin response to an intravenous glucose tolerance test in normal man. J Endocrinol Invest 9, 27–30 (1986). https://doi.org/10.1007/BF03348058
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DOI: https://doi.org/10.1007/BF03348058