title: Peripheral administration of CDP-choline and its cholinergic metabolites increases serum insulin: muscarinic and nicotinic acetylcholine receptors are both involved in their actions.
abstract: 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 micromol/kg) increased serum insulin in a dose- and time-related manner. Equivalent doses (200-600 micromol/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 micromol/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 micromol/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.
authors.affiliation: Department of Biochemistry, Uludag University Medical School, Bursa 16059, Turkey. yesim@uludag.edu.tr
authors.forename: Yesim Ozarda
authors.initials: YO
authors.lastname: Ilcol
authors.forename: Mehmet
authors.initials: M
authors.lastname: Cansev
authors.forename: Mustafa Sertac
authors.initials: MS
authors.lastname: Yilmaz
authors.forename: Emre
authors.initials: E
authors.lastname: Hamurtekin
authors.forename: Ismail H
authors.initials: IH
authors.lastname: Ulus
mesh_terms: D000109:Acetylcholine / Q000737:chemistry / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002794:Choline / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007328:Insulin / Q000097:blood* / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010767:Phosphorylcholine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000317:Adrenergic alpha-Antagonists; D007328:Insulin; D018733:Nicotinic Antagonists; D011942:Receptors, Adrenergic, alpha; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D010767:Phosphorylcholine; D003566:Cytidine Diphosphate Choline; D002794:Choline; D000109:Acetylcholine