Peripheral administration of CDP-choline and its cholinergic metabolites increases serum insulin: Muscarinic and nicotinic acetylcholine receptors are both involved in their actions

Ilcol Y. O. , CANSEV M., YILMAZ M. S. , Hamurtekin E., Ulus I. H.

NEUROSCIENCE LETTERS, vol.431, no.1, pp.71-76, 2008 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 431 Issue: 1
  • Publication Date: 2008
  • Doi Number: 10.1016/j.neulet.2007.11.024
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.71-76
  • Keywords: CDP-choline, choline, insulin, glucose, cholinergic, RELEASE, GLUCOSE, RAT, SECRETION, CYTIDINE, CNS
  • Bursa Uludag University Affiliated: Yes


The present study was designed to test the effects of CDP-choline and its metabolites on serum insulin concentrations in rats and to investigate the involvements of cholinergic and adrenergic receptors in the effect. Intraperitoneal (i.p.) administration of CDP-choline (200-600 mu mol/kg) increased serum insulin in a dose- and time-related manner. Equivalent doses (200-600 mu mol/kg; i.p.) of phosphocholine or choline also increased serum insulin dose-dependently. Serum-free choline concentrations increased several-fold following i.p. administration of CDP-choline, phosphocholine or choline itself. In contrast, equivalent doses of cytidine monophosphate and cytidine failed to alter serum insulin concentrations. The increases in serum insulin induced by i.p. 600 mu mol/kg of CDP-choline, phosphocholine or choline were abolished by pretreatment with the ganglionic nicotinic acetylcholine receptor antagonist hexamethonium (15 mg/kg; i.p.), or by the muscarinic receptor antagonist atropine methylnitrate (2 mg/kg; i.p.). Pretreatment with prazosin (0.5 mg/kg; i.p.), an alpha(1)-adrenoceptor antagonist, or yohimbine (5 mg/kg, i.p.), an alpha(2)-adrenoceptor antagonist, enhanced slightly the increases in serum insulin in response to 600 mu mol/kg of CDP-choline, phosphocholine and choline. Serum insulin also increased following central administration of choline; the effect was blocked by intracerebroventricularly injected atropine, mecamylamine or hemicholinium-3 (HC-3). It is concluded that CDP-choline or its cholinergic metabolites phosphocholine and choline increases circulating insulin concentrations by increasing muscarinic and nicotinic cholinergic neurotransmission in the insulin secreting beta-cells. (C) 2007 Elsevier Ireland Ltd. All rights reserved.