Horm Metab Res 2002; 34(6): 341-347
DOI: 10.1055/s-2002-33264
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Intraperitoneal Administration of Choline Increases Serum Glucose in Rat: Involvement of the Sympathoadrenal System

Y.  O.  Ilcol 1 , M.  S.  Gurun 2 , Y.  Taga 3 , I.  H.  Ulus 2
  • 1Department of Biochemistry Marmara University Medical School, Istanbul, Turkey
  • 2Department of Pharmacology and Clinical Pharmacology, Uludag University Medical School, Bursa
  • 3Department of Biochemistry Marmara University Medical School, Istanbul, Turkey
Further Information

Publication History

Received 3 January 2002

Accepted after Revision 20 February 2002

Publication Date:
12 August 2002 (online)

Abstract

Intraperitoneal injection of choline (40, 80 or 120 mg/kg) produced a dose-dependent increase in serum glucose and choline levels in rats. The increases in serum glucose and choline were associated with an increase of serum insulin as well as plasma levels of epinephrine and norepinephrine. The increases in serum glucose and plasma catecholamine concentrations induced by choline (120 mg/kg) were blocked by pretreatment with the ganglionic nicotinic receptor antagonist hexamethonium (15 mg/kg), but were not affected by pretreatment with atropine (5 mg/kg). The choline-induced rise in serum insulin was blocked by pretreatment with atropine and with hexamethonium each. The increase in serum glucose evoked by choline (120 mg/kg) was blocked by α-adrenoceptor blockade and bilateral adrenalectomy each. Blockade of β-adrenoceptor by propranolol or chemical sympathectomy by 6-hydroxydopamine failed to alter the hyperglycemic response to choline. These results show that choline, a precursor of the neurotransmitter acetylcholine, increases serum glucose and insulin levels. The effect of choline on serum insulin is mediated by both muscarinic and nicotinic acetylcholine receptors, whereas the effect of choline on serum glucose is mediated solely by nicotinic receptors. The stimulation of adrenal medullary catecholamine release and subsequent activation of α-adrenoceptors apparently mediates the hyperglycemic effect of choline.

References

  • 1 Ahrén B. Autonomic regulation of islet hormon secretion - implications for health and disease.  Diabetologia. 2000;  43 393-410
  • 2 Alvarez X A, Laredo M, Corzo D, Fernadez-Novoa L, Mouzo R, Perea J, Daniele D, Cacabelos R. Citicoline improves memory performance in elderly subjects.  Methods Find Exp Clin Pharmacol. 1997;  19 201-210
  • 3 Alvarez X A, Mouzo R, Pichel V, Perez P, Laredo M, Fernadez-Novoa L, Corzo L, Zas R, Alcaraz M, Secades J J, Lozano R, Cacabelos R. Double-blind placebo-controlled study with citicoline in APO-E genotyped Alzheimer’s disease patients. Effects on cognitive performance, brain bioelectrical activity and cerebral perfusion.  Methods Find Exp Clin Pharmaol. 1999;  21 633-644
  • 4 Arslan B Y, Ulus I H, Savci V, Kiran B K. Effects of intracerebroventricular injected choline on cardiovascular functions and sympathoadrenal activity.  J Cardiovasc Pharmacol. 1991;  17 814-821
  • 5 Buyukuysal R L, Ulus I H, Aydin S, Kiran B K. 3,4-Diaminopyridine and choline increases in vivo acetylcholine release in rat striatum.  Eur J Pharmacol. 1995;  281 179-185
  • 6 Caamano J, Gomez M J, Franco A, Cacabelos R. Effects of CDP-choline on cognition and cerebral hemodynamics in patients with Alzheimer’s disease.  Methods Find Exp Clin Pharmaol. 1994;  16 211-218
  • 7 Cacabelos R, Caamano J, Gomez M J, Fernandez-Novoa L, Franco-Maside A, Alvarez X A. Therapeutic effects of CDP-choline in Alzheimer’s disease. Cognition, brain mapping, cerebrovascular hemodynamics, and immune factors.  Ann NY Acad Sci. 1996;  17 399-403
  • 8 Clark W M, Williams B J, Selzer K A, Zweifler R M, Sabunjian L A, Gammans R E. A randomized efficacy trial of citicoline in patients with acute ischemic stroke.  Stroke. 1999;  30 2592-2597.
  • 9 Coppes R P, Brouwer F, Freie I, Smit J, Zaagsma J. Sustained prejunctional facilitation of noradrenergic neurotransmission by epinephrine as a co-transmitter in the portal vein of freely moving rats.  Br J Pharmacol. 1994;  113 342-344
  • 10 Dolezal V, Tucek S. Effects of choline and glucose on atropine-induced alterations of acetylcholine synthesis and content in the caudate nuclei of rats.  Brain Res. 1982;  240 285-293
  • 11 Farber S A, Kischka U, Marsall D L, Wurtman R J. Potentiation by choline of basal and electrically-evoked acetylcholine release, as studied using a novel device which both stimulates and perfuses rat corpus striatum.  Brain Res. 1993;  607 177-184
  • 12 Gilon P, Henquin J C. Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function.  Endoc Rev. 2001;  22 565-604
  • 13 Gold P E. Role of glucose in regulating the brain and cognition.  Am J Clin Nutr. 1995;  61 987S-995S
  • 14 Gold P E, Vogt J, Hall J L. Glucose effect of memory: behavioral and pharmacological characteristics.  Behav Neural Biol. 1986;  46 145-155
  • 15 Gurun M S, Savci V, Kiran B K, Ulus I H. Centrally administered choline increases plasma prolactin levels in concious rats.  Neuroscience Lett. 1997;  232 79-82
  • 16 Karlsson S, Ahrén B. Muscarinic receptor subtypes in carbachol-stimulated insulin and glucagon secretion in the mouse.  J Auton Pharmacol. 1993;  342 291-295
  • 17 Karlsson S, Ahrén B. Insulin and glucagon secretion by ganglionic nicotinic activation in adrenalectomized mice.  Eur J Pharmacol. 1998;  342 291-295
  • 18 Kopf S R, Baratti C M. Memory-improving actions of glucose: involvement of a central cholinergic mechanism.  Behav Neural Biol. 1994;  62 237-243.
  • 19 Kopf S R, Buchholzer M, Hilgert M, Löffelholz K, Klein J. Glucose plus choline improves passive avoidance behaviour and increase hippocampal acetylcholine release in mice.  Neuroscience. 2001;  103 365-371
  • 20 Köppen A, Klein J, Erb C, Löffelholz K. Acetylcholine release and choline availability in the rat hippocampus. Effects of exogenous choline and nicotinamide.  J Pharmacol Exp Ther. 1997;  282 1139-1145
  • 21 Levin H S. Treatment of postconcussional symptoms with CDP-choline.  J Neurol Sci. 1991;  103 (Suppl.) S39-S42
  • 22 Lozano R. CDP-choline in the treatment of cranio-cephalic trauma.  J Neurol Sci. 1991;  103 (Suppl.) S43-S47
  • 23 Lundquist I. Cholinergic muscarinic effects on insulin release in mice.  Pharmacology. 1982;  25 338-347
  • 24 Manning C A, Ragozzino M E, Gold P E. Glucose enhancement of memory in patients with probable senile dementia of the Alzheimer type.  Neurobiol Aging. 1993;  14 523-528
  • 25 Manning C A, Honn V J, Stone W S, Jane J S, Gold P E. Glucose effects on cognition in adults with Down’s syndrome.  Neuropsychology. 1998;  12 479-484
  • 26 Messier C, Gagnon M. Glucose regulation and cognitive functions relation to Alzheimer’s disease and diabetes.  Behav Brain Res. 1996;  75 1-11
  • 27 Niijima A. Nervous regulation of metabolism.  Prog Neurobiol. 1989;  33 135-147
  • 28 Ragozzino M E, Unick K E, Gold P E. Hippocampal acetylcholine release during memory testing in rats: augmentation by glucose.  Proc Natl Acad Sci USA. 1996;  93 4693-4698
  • 29 Savci V, GurunS , Ulus I H, Kiran B K. Intracerebroventricular injection of choline increases plasma oxytocin levels in concious rats.  Brain Res. 1996;  709 97-102
  • 30 Savci V, Gurun M S, Ulus I H, Kiran B K. Effect of intracerebroventricularly injected choline on plasma ACTH and β-endorphin levels in concious rats.  Eur J Pharmacol. 1996;  309 275-280
  • 31 Scally M C, Ulus I H, Wurtman R J. Choline administration to rat increases urinary catecholamines.  J Neural Trans. 1978;  43 103-112
  • 32 Scheurink A JW, Steffens A B, Benthem L. Central and peripheral adrenoceptors affect glucose, free fatty acids, and insulin in exercising rats.  Am J Physiol. 1988;  255 R547-R556
  • 33 Spiers P A, Myers D, Hochanadel G S, Lieberman H R, Wurtman R J. Citicoline improves verbal memory in aging.  Arch Neurol. 1996;  53 441-448
  • 34 Stagner J I, Samols E. Modulation of insulin secretion by pancreatic ganglionic nicotinic receptors.  Diabetes. 1986;  35 849-855
  • 35 Strubbe J H, Steffens A B. Neural control of insulin secretion.  Horm Metab Res. 1993;  25 507-512
  • 36 Tucek S. Short-term control of the synthesis of acetylcholine.  Prog Biophys Molec Biol. 1993;  60 59-69
  • 37 Unal C B, Demiral Y, Ulus I H. The effects of choline on body temperature in concious rats.  Eur J Pharmacol. 1999;  363 121-126
  • 38 Ulus I H, Arslan B Y, Savci V, Kiran B K. Restoration of blood pressure by choline treatment in rats made hypotensive by haemorrhage.  Br J Pharmacol. 1995;  116 1911-1917
  • 39 Ulus I H, Hirsch M J, Wurtman R J. Trans-synaptic induction of adrenomedullary tyrosine hydroxylase activity by choline: evidence that choline administration can increase cholinergic transmission.  Proc Natl Acad Sci USA. 1977;  74 798-800
  • 40 Ulus I H, Scally M C, Wurtman R J. Enhancement by choline of the induction of adrenal tyrosine hydroxylase by phenoxybenzamine, 6-hydroxydopamine, insulin and exposure to cold.  J Pharmacol Exp Ther. 1978;  204 676-682
  • 41 Ulus I H, Millington W R, Buyukuysal R L, Kiran B K. Choline as an agonist: determination of its agonistic potency on cholinergic receptors.  Biochem Pharmacol. 1988;  37 2747-2755
  • 42 Ulus I H, Wurtman R J. Choline administration: activation of tyrosine hydroxylase in dopaminergic neurons of rat brain.  Science. 1976;  194 1060-1061
  • 43 Ulus I H, Wurtman R J, Mauron C, Blusztajn J K. Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum.  Brain Res. 1989;  484 217-227
  • 44 Wang F L, Haubrich D L. A simple, sensitive and specific assay for free choline in plasma.  Anal Biochem. 1975;  63 195-201
  • 45 Yamaguchi N. Sympathoadrenal system in neuroendocrine control of glucose: mechanisms involved in the liver, pancreas, and adrenal gland under hemorrhagic and hypoglycemic stress.  Can J Physiol Pharmacol. 1992;  70 167-206

Prof. Dr. I. H. Ulus

Department of Pharmacology and Clinical Pharmacology · Uludag University Medical School

Bursa · Turkey ·

Phone: + 90 (224) 442 8190

Fax: + 90 (224) 442 8189

Email: ihulus@uludag.edu.tr