Abstract
Background: Many gastrointestinal complications in diabetes are connected to neurohumoral dysfunction resulting in abnormalities of intestinal motility, secretion and absorption. Minerals have been reported as essential cofactors for basic cellular reactions but there is dearth of information on effect of Magnesium on gastrointestinal transit time (GITT) and the mechanism of action.
Methods: Sixty male albino Wistar rats (180 – 200g) were grouped into twelve of five animals each. Group 1 (control) received 0.2ml saline. Groups 2-6 were normal rats treated with magnesium sulphate (as magnesium) (500mg/kg), adrenaline (0.5mg/kg), magnesium (500mg/kg) and adrenaline (0.5mg/kg), prazosin (1mg/kg) and both magnesium (500mg/kg) and prazosin (1mg/kg) respectively. Groups 7 - 12 were diabetic rats treated as in groups 1- 6. Diabetes was induced intraperitoneally with alloxan (120mg/kg bwt).
Results: There was significant (p<0.05) reduction in GITT index in normal rats treated with magnesium, prazosin and combination of magnesium and prazosin compared with control. Treatment with adrenaline alone produced significant increase in GITT. However treatment with both magnesium and adrenaline produced significant reduction compared with control. This reduction in GITT was similar to that obtained in magnesium only and prazosin only treated groups. Diabetic groups showed significant reduction in GITT in all treated groups except the adrenaline only treated group which produced significant increase in GITT.
Conclusion: The significant reduction in GITT produced by magnesium in both normal and diabetic animals was comparable to that produced by prazosin (an α1 -adrenoceptor antagonist) indicating that magnesium may be inhibiting gastrointestinal smooth muscle contraction through α1 -adrenoceptor antagonist pathway.
Keywords: Gastrointestinal transit time, diabetes mellitus, magnesium, adrenaline, Prazosin.
Résumé
Contexte: Beaucoup de complications gastro-intestinales chez les diabétiques sont liées à une dysfonction neurohumoral entraînant des anomalies de la motilité, la sécrétion et l’absorption intestinale. Les minéraux ont été présentés comme des co-facteurs essentiels nécessaires aux réactions cellulaires élémentaires, mais il ya peu d’informations sur l’effet du magnésium sur le temps du transit gastro-intestinal (GITT) et le mécanisme d’action.
Méthodes: Soixante rats Wistar mâles albinos (180 - 200g) ont été divisés en douze groupes de cinq animaux. Le groupe 1 (pilote) a reçu 0,2 ml de solution saline. Les groupes de 2-6 sont des rats normaux qui ont reçu de la sulfate de magnésium (en tant que magnésium) (500mg/kg), de l’adrénaline (0,5mg/kg), du magnésium (500mg/kg) et de l’adrénaline (0,5mg/kg), de la prazosine (1mg/kg) ; du magnésium (500mg/kg) et de la prazosine (1mg/kg) respectivement. Les groupes 7 à 12 sont des rats diabétiques traités comme dans les groupes 1 à 6. Le diabète a été induit par voie intra-péritonéale avec l’alloxane (120mg/kg pc).
Résultats: Il y avait une réduction importante (P <0,05) de l’indice GITT chez les rats normaux traités avec du magnésium, de la prazosine et de la combinaison de magnésium et de la prazosine par rapport aux rats pilotes. Le traitement par l’adrénaline seulement donne une augmentation importante de GITT. Cependant, le traitement avec du magnésium et de l’adrénaline ont donné une réduction significative comparativement aux rats pilotes. Cette réduction de la GITT était similaire au cas des groupes traités uniquement au magnésium et uniquement à la prazosine. Les groupes des rats diabétiques ont affiché une réduction importante en GITT dans tous les groupes traités, sauf dans le groupe traité uniquement à l’adrénaline qui a affiché une augmentation importante en GITT.
Conclusion: La réduction remarquable en GITT produite par le magnésium chez les animaux normaux et diabétiques était comparable à celle produite par la prazosine (antagoniste á1-adrénergique) indiquant que le magnésium peut inhiber la contraction du muscle lisse gastro-intestinal par la voie antagoniste á1-adrénergiques.
Correspondence: Dr. Elsie O. Adewoye, Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria. E-mail: elolade@yahoo.com
References
Kamm MA: Why the enteric nervous system is important to clinicians. Gut 2000; 47 Suppl 4: iv8-iv9; discussion iv10.
Feldman M and Schiller LR: Disorders of gastrointestinal motility associated with Diabetes Mellitus. Ann Med 1983; 98: 378-384.
Wolosin JD: Diabetes and the Gastrointestinal Tract; Clin. Diabetes 2000; 18(4):159-169.
Narbonne H, Paquis-Fluckinger V, Valero R, et al. Gastrointestinal tract symptoms in Maternally Inherited Diabetes and Deafness (MIDD) Diabetes Metab. 2004; 30(1):61-66.
Björnsson ES, Urbanavicius V, Eliasson B, et al. Effects of Hyperglycemia on Interdigestive Gastrointestinal Motility in Humans. Scandinavian J. Gastroenterol. 1994; 29 (12): 1096-1104
Rayner CK and Horowitz M: Gastrointestinal motility and glycemic control in diabetes: the Chicken and the Egg revisited. J Clin Invest. 2006; 116 (2): 299 – 302.
Ghosh MN: Quantitative study of antagonists on isolated preparation. In: Ghosh, ed. Fundamentals of experimental Pharmacolgy 3rd ed. Kolkata, Hilton and Company, 2005; pp 134 – 147.
Shills ME, Olson JA, Shike M and Ross AC, Eds: Modern Nutrition in Health and Disease. 9thedition. Philadelphia Pa., Lea and Febiger: 1999
Liao F, Folsom A and Brancati F: Is low magnesium concentration a risk factor for coronary heart disease? The Atherosclerosis Risk in Communities (ARIC) Study. American Heart Journal: 1998; 136(3):480-490.
Lopez-Ridaura R, Willett WC, Rimm EB et al:
Magnesium Intake and Risk of Type 2 Diabetes in Men and Women. Diabetes Care: 2004; 27(1): 134-140.
Abayomi AI, Adewoye EO, Olaleye SB and Salami AT: Effect of Magnesium pre-treatment on Alloxan induced hyperglycemia in rats. African Health Sciences: 2011; 11 (1): 483 – 489.
National Institute of Health: Guide for the Care and Use of Laboratory Animals. NIH publication: 1985; 85-93.
Dhande PP, Ranade RS and Ghonane BB: Effect of Magnesium oxide on the activity of standard anti epileptic drugs against experimental seizures in rats. Indian J. Pharmacol; 2009; 41(6): 268 - 272
Coderre TJ, Basbaum AI, Helms C and Levine JD: High-dose epinephrine acts at alpha 2-adrenoceptors to suppress experimental arthritis. Brain Res.; 1991; 544(2):325-328.
Borchard RE: Drug Dosage in Laboratory Animals, A Handbook, 382, 3rd edition. CRC Press: 1992.
Sandhiya S, Dkhar SA, Krishna PRM and Ramaswamy S: Role of ion channel modifiers in reversal of morphine-induced gastrointestinal inertia by prokinetic agents in mice. Indian J Exp Biol. 2008; 46: 60 – 65
Tembhurne SV and Sakarkar DM: Effect of Murraya Koenigii leaves Extracts on Gastrointestinal motility: Involving Calcium Channel Innervation in Mice. Arch Pharm Sci and Res: 2009; 1(2): 189 -193
Szkudelski T: The Mechanism of Alloxan and Streptozotocin action in B Cells of the Rat Pancreas. Physiol. Res. 2001; 50: 536 – 546.
Chesta J, Debnam ES, Srai SKS and Epstein O: Delayed stomach to caecum transit time in the diabetic rat. Possible role of hyperglucagonaemia Gut: 1990; 31: 660-662
Reddy PMK, Dkhar SA and Subramanian R: Effect of insulin on small intestinal transit in normal mice is independent of blood glucose level. BMC Pharmacology, 2006; (6):4 – 11.
Anjaneyulu M and Ramarao, P: Studies on gastrointestinal tract functional changes in diabetic animals. Methods Find Exp Clin. Pharmacol: 2002; 24: 71-75.
Adewoye EO, Ige AO and Latona CT: Effect of Methanolic extract of Musa sapientum leaves on Gastrointestinal Transit time in Normal and Alloxan induced Diabetic rats: Possible Mechanism of Action. Nig. J. Physiol. Sci. 2011; 26(June) 83 – 88.
Toda N and Tfelt-Hnsen P: Calcium antagonists in migraine prophylaxis. In: Olesen J Goads by PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA, eds. The Headaches, 3rdedn. Philadelphia, PA: LippincottWilliamsWilkins: 2006; 539-544.
Garcia LA, DeJong SC, Martin SM, et al. Magnesium reduces free radicals in an in vivo coronary occlusion-reperfusion. J. Am. Coll. Cardiol.; 1998; 32; 536-539.
Ruwart MJ, Klepper MS and Rush BD: Regulation of gastric emptying, small intestinal transit and colonic transit in the rat. Gastroenterology, 1979a; 76, 1232
Wakabayashi I, Hatake K, Kakishita E, Hishida S and Nagai K: Desensitization of alpha-1 adrenergic receptor mediated smooth muscle contraction in aorta from endotoxic rats. Life Sci.: 1989; 45(6):509-515.
De Ponti F, Giaroni C, Cosentino M, Lecchini S and Frigo G: Calcium channel blockers and gastrointestinal motility: Basic and clinical aspects. Pharmacol Ther. 1993; 60(1), 121–148.
Barbagallo M, Dominguez LJ, Bardicef O and Resnick LM: Altered Cellular Magnesium Responsiveness to Hyperglycemia in Hypertensive Subjects. Hypertension 2001; 38:612 – 615.
Fontaine J, Grivegnee A and Reuse J : Adrenoceptors and regulation of intestinal tone in the isolated colon of the mouse. Br J Pharmacol 1984; 81(2) 231-243.