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Antidepressant effect of taurine in diabetic rats

Amino Acids volume 43, pages 1525–1533 (2012)Cite this article

Abstract

Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

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References

  • Albrecht J, Schousboe A (2005) Taurine interaction with neurotransmitter receptors in the CNS: an update. Neurochem Res 30:1615–1621

    PubMed  Article  CAS  Google Scholar 

  • Anjaneyulu M, Chopra K, Kaur I (2003) Antidepressant activity of quercetin, a bioflavonoid, in streptozotocin-induced diabetic mice. J Med Food 6:391–395

    PubMed  Article  CAS  Google Scholar 

  • Biessels GJ, van der Heide LP, Kamal A, Bleys RL, Gispen WH (2002) Aging and diabetes: implications for brain function. Eur J Pharmacol 441:1–14

    PubMed  Article  CAS  Google Scholar 

  • Birdsall TC (1998) Therapeutic applications of taurine. Altern Med Rev 3:128–136

    PubMed  CAS  Google Scholar 

  • Bonner-Weir S (2000) Life and death of the pancreatic beta cells. Trends Endocrinol Metab 11:375–378

    PubMed  Article  CAS  Google Scholar 

  • Brambilla P, Perez J, Barale F, Schettini G, Soares JC (2003) GABAergic dysfunction in mood disorders. Mol Psychiatry 8:721–737

    PubMed  Article  CAS  Google Scholar 

  • Bustamante J, Lobo MV, Alonso FJ, Mukala NT, Gine E, Solis JM, Tamarit-Rodriguez J, Martin del Rio R (2001) An osmotic-sensitive taurine pool is localized in rat pancreatic islet cells containing glucagon and somatostatin. Am J Physiol Endocrinol Metab 281:E1275–E1285

    PubMed  CAS  Google Scholar 

  • Carneiro EM, Latorraca MQ, Araujo E, Beltrá M, Oliveras MJ, Navarro M, Berná G, Bedoya FJ, Velloso LA, Soria B, Martín F (2009) Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem 20:503–511

    PubMed  Article  CAS  Google Scholar 

  • Champaneri S, Wand GS, Malhotra SS, Casagrande SS, Golden SH (2010) Biological basis of depression in adults with diabetes. Curr Diab Rep 10:396–405

    PubMed  Article  CAS  Google Scholar 

  • Chen SW, Kong WX, Zhang YJ, Li YL, Mi XJ, Mu XS (2004) Possible anxiolytic effects of taurine in the mouse elevated plus-maze. Life Sci 75:1503–1511

    PubMed  Article  CAS  Google Scholar 

  • Cherif H, Reusen B, Ahn MT, Hoet JJ, Remacle C (1998) Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low protein diet. J Endocrinol 159:341–348

    PubMed  Article  CAS  Google Scholar 

  • Daneman D (2006) Type 1 diabetes. Lancet 367:847–858

    PubMed  Article  CAS  Google Scholar 

  • de Boer T, Bartels K, Metselaar HJ, Bruinvels J (1980) Di-n-propylacetate-induced abstinence behaviour as a possible correlate of increased GABA-ergic activity in the rat. Psychopharmacology 71:257–267

    PubMed  Article  Google Scholar 

  • Del Prato S, Marchetti P (2004) Beta- and alpha-cell dysfunction in type 2 diabetes. Horm Metab Res 36:775–781

    PubMed  Article  Google Scholar 

  • El Idrissi A, Trenkner E (2004) Taurine as a modulator of excitatory and inhibitory neurotransmission. Neurochem Res 29:189–197

    PubMed  Article  CAS  Google Scholar 

  • El Idrissi A, Messing J, Scalia J, Trenkner E (2003) Prevention of epileptic seizures by taurine. Adv Exp Med Biol 526:515–525

    PubMed  Article  CAS  Google Scholar 

  • El Idrissi A, Boukarrou L, Heany W, Malliaros G, Sangdee C, Neuwirth L (2009) Effects of taurine on anxiety-like and locomotor behavior of mice. Adv Exp Med Biol 643:207–215

    PubMed  Article  CAS  Google Scholar 

  • Franconi F, Bennardini F, Mattana A, Miceli M, Ciuti M, Mian M, Gironi A, Anichini R, Seghieri G (1995) Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation. Am J Clin Nutr 61:1115–1119

    PubMed  CAS  Google Scholar 

  • Franconi F, Miceli M, Fazzini A, Seghieri G, Caputo S, DiLeo MA, Lepore D, Ghirlanda G (1996) Taurine and diabetes. Humans and experimental models. Adv Exp Med Biol 403:579–582

    PubMed  CAS  Google Scholar 

  • Gavard JA, Lustman PJ, Clouse RE (1993) Prevalence of depression in adults with diabetes. Diabetes Care 16:1167–1178

    PubMed  Article  CAS  Google Scholar 

  • Gavrovskaya LK, Ryzhova OV, Safonova AF, Matveev AK, Sapronov NS (2008) Protective effect of taurine on rats with experimental insulin-dependent diabetes mellitus. Bull Exp Biol Med 146:226–228

    PubMed  Article  CAS  Google Scholar 

  • Gilon P, Bertrand G, Loubatieres-Mariani MM, Remacle C, Henquin JC (1991) The influence of gamma-aminobutyric acid on hormone release by the mouse and rat endocrine pancreas. Endocrinology 129:2521–2529

    PubMed  Article  CAS  Google Scholar 

  • Gomez R, Barros HM (2000) Ethopharmacology of the antidepressant effect of clonazepam in diabetic rats. Pharmacol Biochem Behav 66:329–335

    PubMed  Article  CAS  Google Scholar 

  • Gomez R, Vargas CR, Wajner M, Barros HM (2003) Lower in vivo brain extracellular GABA concentration in diabetic rats during forced swimming. Brain Res 968:281–284

    PubMed  Article  CAS  Google Scholar 

  • Hansen SH (2001) The role of taurine in diabetes and the development of diabetes complications. Diabetes Metab Res Rev 17:330–346

    PubMed  Article  CAS  Google Scholar 

  • Houston AJ, Wong JC, Ebenezer IS (2002) Effects of subcutaneous administration of the gamma-aminobutyric acid(A) receptor agonist muscimol on water intake in water-deprived rats. Physiol Behav 77:445–450

    PubMed  Article  CAS  Google Scholar 

  • Hruska RE, Thut PD, Huxtable RJ, Bressler R (1975) Suppression of conditioned drinking by taurine and related compounds. Pharmacol Biochem Behav 3:593–599

    PubMed  Article  CAS  Google Scholar 

  • Ichihara K, Nabeshima T, Kameyama T (1988) Opposite effects induced by low and high doses of apomorphine on single-trial passive avoidance learning in mice. Pharmacol Biochem Behav 30:107–113

    PubMed  Article  CAS  Google Scholar 

  • Jia F, Yue M, Chandra D, Keramidas A, Goldstein PA, Homanics GE, Harrison NL (2008) Taurine is a potent activator of extrasynaptic Gaba A receptors in the thalamus. J Neurosci 28:106–115

    PubMed  Article  CAS  Google Scholar 

  • Kulakowski EC, Maturo J (1984) Hypoglycemic properties of taurine: not mediated by enhanced insulin release. Biochem Pharmacol 33:2835–2838

    PubMed  Article  CAS  Google Scholar 

  • L’Amoreaux WJ, Cuttitta C, Santora A, Blaize JF, Tachjadi J, El Idrissi A (2010a) Taurine regulates insulin release from pancreatic beta cell lines. J Biomed Sci 17:S11

    PubMed  Article  Google Scholar 

  • L’Amoreaux WJ, Marsillo A, El Idrissi A (2010b) Pharmacological characterization of GABAA receptors in taurine-fed mice. J Biomed Sci 17(S1):S14

    PubMed  Article  Google Scholar 

  • Levinskaya N, Trenkner E, El Idrissi A (2006) Increased GAD-positive neurons in the cortex of taurine-fed mice. Adv Exp Med Biol 583:411–417

    PubMed  Article  CAS  Google Scholar 

  • Luscher B, Shen Q, Sahir N (2011) The GABAergic deficit hypothesis of major depressive disorder. Mol Psychiatry 16:383–406

    PubMed  Article  CAS  Google Scholar 

  • Lustman PJ, Clouse RE (2005) Depression in diabetic patients: the relationship between mood and glycemic control. J Diabetes Complicat 19:113–122

    PubMed  Google Scholar 

  • Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE (2000) Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care 23:934–942

    PubMed  Article  CAS  Google Scholar 

  • Medina JH, DeRobertis E (1984) Taurine modulation of the benzodiazepine gamma–aminobutyric acid receptor complex in brain membranes. J Neurochem 42:1212–1217

    PubMed  Article  CAS  Google Scholar 

  • Moriguchi S, Shioda N, Han F, Yeh JZ, Narahashi T, Fukunaga K (2009) Galantamine enhancement of long-term potentiation is mediated by calcium/calmodulin-dependent protein kinase II and protein kinase C activation. Hippocampus 19:844–854

    PubMed  Article  CAS  Google Scholar 

  • Morishita S (2009) Clonazepam as a therapeutic adjunct to improve the management of depression: a brief review. Hum Psychopharmacol 24:191–198

    PubMed  Article  CAS  Google Scholar 

  • Murakami T, Furuse M (2010) The impact of taurine- and beta-alanine-supplemented diets on behavioral and neurochemical parameters in mice: antidepressant versus anxiolytic-like effects. Amino Acids 39:427–434

    PubMed  Article  CAS  Google Scholar 

  • Nin MS, Salles FB, Azeredo LA, Frazon AP, Gomez R, Barros HM (2008) Antidepressant effect and changes of GABAA receptor gamma2 subunit mRNA after hippocampal administration of allopregnanolone in rats. J Psychopharmacol 22:477–485

    PubMed  Article  CAS  Google Scholar 

  • Oja SS, Saransaari P (2007) Pharmacology of taurine. Proc West Pharmacol Soc 50:8–15

    PubMed  CAS  Google Scholar 

  • Perry TL, Bratty PJ, Hansen S, Kennedy J, Urquhart N, Dolman CL (1975) Hereditary mental depression and Parkinsonism with taurine deficiency. Arch Neurol 32:108–113

    PubMed  Article  CAS  Google Scholar 

  • Porsolt RD, Bertin A, Jalfre M (1977) Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 229:327–336

    PubMed  CAS  Google Scholar 

  • Ribeiro RA, Bonfleur ML, Amaral AG, Vanzela EC, Rocco SA, Boschero AC, Carneiro EM (2009) Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets. Diabetes Metab Res Rev 25:370–379

    PubMed  Article  CAS  Google Scholar 

  • Sanacora G, Saricicek A (2007) GABAergic contributions to the pathophysiology of depression and the mechanism of antidepressant action. CNS Neurol Disord Drug Targets 6:127–140

    PubMed  Article  CAS  Google Scholar 

  • Sanberg PR, Ossenkopp KP (1977) Dose–response effects of taurine on some open-field behaviors in the rat. Psychopharmacology (Berlin) 53(2):207–209

    Article  CAS  Google Scholar 

  • Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99

    PubMed  Article  CAS  Google Scholar 

  • Sen S, Sanacora G (2008) Major depression: emerging therapeutics. Mt Sinai J Med 75:204–225

    PubMed  Article  Google Scholar 

  • Singh-Franco D, Robles G, Gazze D (2007) Pramlintide acetate injection for the treatment of type 1 and type 2 diabetes mellitus. Clin Ther 29:535–562

    PubMed  Article  CAS  Google Scholar 

  • Smith WT, Londborg PD, Glaudin V, Painter JR (2002) Is extended clonazepam cotherapy of fluoxetine effective for outpatients with major depression? J Affect Disord 70:251–259

    PubMed  Article  CAS  Google Scholar 

  • Smith LA, Cornelius VR, Azorin JM, Perugi G, Vieta E, Young AH, Bowden CL (2010) Valproate for the treatment of acute bipolar depression: systematic review and meta-analysis. J Affect Disord 122:1–9

    PubMed  Article  CAS  Google Scholar 

  • Sung MJ, Chang KJ (2009) Dietary taurine and nutrients intake and anthropometric and body composition data by abdominal obesity in Korean male college students. Adv Exp Med Biol 643:429–435

    PubMed  Article  CAS  Google Scholar 

  • Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH et al (1995) Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats. Am J Physiol 269:429–438

    Google Scholar 

  • Tsuboyama-Kasaoka N, Shozawa C, Sano K, Kamei Y, Kasaoka S, Hosokawa Y, Ezaki O (2006) Taurine (2-aminoethanesulfonic acid) deficiency creates a vicious circle promoting obesity. Endocrinology 147:3276–3284

    PubMed  Article  CAS  Google Scholar 

  • Vargas C, Tannhauser M, Tannhauser SL, Barros HM (1996) Lithium and valproate combined administration: acute behavioural effects and drug plasma levels. Pharmacol Toxicol 79:87–91

    PubMed  Article  CAS  Google Scholar 

  • Walsh RN, Cummins RA (1976) The Open-Field Test: a critical review. Psychol Bull 83:482–504

    PubMed  Article  CAS  Google Scholar 

  • Whirley BK, Einat H (2008) Taurine trials in animal models offer no support for anxiolytic, antidepressant or stimulant effects. Isr J Psychiatry Relat Sci 45:11–18

    PubMed  Google Scholar 

  • Wolffenbuttel BH, van Haeften TW (1995) Prevention of complications in non-insulin-dependent diabetes mellitus (NIDDM). Drugs 50:263–288

    PubMed  Article  CAS  Google Scholar 

  • Wu JY, Prentice H (2010) Role of taurine in the central nervous system. J Biomed Sci 17:S1

    PubMed  Article  Google Scholar 

  • Zhang M, Bi LF, Fang JH, Su XL, Da GL, Kuwamori T, Kagamimori S (2004) Beneficial effects of taurine on serum lipids in overweight or obese non-diabetic subjects. Amino Acids 26:267–271

    PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA) and Conselho Nacional de Desenvolvimento Científico e Tecnológico, CNPq. G.C. and H.B. receives a fellowship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, CAPES, and H.B. received a CNPq 1C Researcher Productivity Grant.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Programa de Pós Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil

    Greice Caletti, Danielly B. Olguins, Helena M. T. Barros & Rosane Gomez

  2. Departamento de Ciências da Saúde, Disciplina de Farmacologia, Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Porto Alegre, Brazil

    Elis F. Pedrollo & Helena M. T. Barros

  3. Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul (UFRGS), Rua Sarmento Leite, 500/202, Porto Alegre, RS, 90050-170, Brazil

    Rosane Gomez

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  1. Greice Caletti
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Caletti, G., Olguins, D.B., Pedrollo, E.F. et al. Antidepressant effect of taurine in diabetic rats. Amino Acids 43, 1525–1533 (2012). https://doi.org/10.1007/s00726-012-1226-x

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Keywords

  • Water intake
  • Food intake
  • GABA agonist
  • Depression
  • Glycemia