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Taurine Supplementation Enhances Insulin Secretion Without Altering Islet Morphology in Non-obese Diabetic Mice

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Book cover Taurine 9

Abstract

Taurine (TAU) is a sulfated amino acid that improves pancreatic islet function and regulates β-cell mass in pre- and diabetic states. We herein analyzed glucose homeostasis and islet morphofunction in non-obese diabetic (NOD) mice supplemented with 2 % TAU in their drinking water from birth until 90-days of age. TAU-supplemented female NOD mice (TAU group) showed a better glucose tolerance without modification in insulinemia, when compared to non-supplemented NOD mice (CTL). Glucose-induced insulin secretion was higher in islets isolated from female and male TAU groups. In addition, a better insulin release was observed at 30 mM K+ in islets from female TAU mice. These effects were accompanied by a higher total intracellular Ca2+ concentration in islets from female and male TAU mice. TAU-treated mice did not show any alteration in β-cell and islet areas, compared with CTL mice. Islets from TAU female mice presented a higher ratio of phosphorylated Akt and ERK (extracellular signal-regulated kinase) related to Akt and ERK protein content, respectively, in comparison with CTL islets. Additional experiments using isolated islets from Swiss mice showed that 3 mM TAU prevented the reduction in insulin secretion induced by 12 h incubation with IL1-β or IL1-β + IFN-γ. In conclusion, TAU supplementation improved NOD islet function without altering endocrine pancreatic morphometry, an effect that may be associated with a protective TAU effect upon cytokine-induced islet dysfunction, together with an improved protein expression of Akt and ERK.

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Abbreviations

Akt:

thymoma viral proto-oncogene/protein kinase B

AUC:

Area under curve

BSA:

Bovine serum albumin

CHOL:

Cholesterol

CTL:

Control

[Ca2+]i :

Intracellular Ca2+ concentration

ERK:

Extracellular signal-regulated kinase

Iκ-Bα:

Inhibitor of nuclear factor kappa B α

IFN-γ:

Interferon γ

IL:

Interleukin

ipGTT:

Intraperitoneal glucose tolerance test

IGF:

Insulin-like growth factor

IR:

Insulin receptor

IRS:

IR substrates

KRB:

Krebs-Ringer bicarbonate

NOD:

Non-obese diabetic

NEFA:

Non-esterified fatty acids

NFκB:

Nuclear factor kappa B

RIA:

Radioimmunoassay

STAT:

Signal transducers and activators of transcription

TAU:

Taurine

TG:

Triglycerides

TNF-α:

Tumor necrosis fator α

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

References

  • Aerts L, Van Assche FA (2001) Low taurine, gamma-aminobutyric acid and carnosine levels in plasma of diabetic pregnant rats: consequences for the offspring. J Perinat Med 29(1):81–84

    Article  CAS  PubMed  Google Scholar 

  • Alvino CL, Ong SC, McNeil KA, Delaine C, Booker GW, Wallace JC, Forbes BE (2011) Understanding the mechanism of insulin and insulin-like growth factor (IGF) receptor activation by IGF-II. PLoS One 6(11):e27488. doi:10.1371/journal.pone.0027488

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Amrani A, Durant S, Throsby M, Coulaud J, Dardenne M, Homo-Delarche F (1998) Glucose homeostasis in the nonobese diabetic mouse at the prediabetic stage. Endocrinology 139(3):1115–1124

    CAS  PubMed  Google Scholar 

  • Anuradha CV, Balakrishnan SD (1999) Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance. Can J Physiol Pharmacol 77(10):749–754

    Article  CAS  PubMed  Google Scholar 

  • Arany E, Strutt B, Romanus P, Remacle C, Reusens B, Hill DJ (2004) Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice. Diabetologia 47(10):1831–1837

    Article  CAS  PubMed  Google Scholar 

  • Batista TM, Ribeiro RA, da Silva PM, Camargo RL, Lollo PC, Boschero AC, Carneiro EM (2013) Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet. Mol Nutr Food Res 57(3):423–434. doi:10.1002/mnfr.201200345

    Article  CAS  PubMed  Google Scholar 

  • Boujendar S, Arany E, Hill D, Remacle C, Reusens B (2003) Taurine supplementation of a low protein diet fed to rat dams normalizes the vascularization of the fetal endocrine pancreas. J Nutr 133(9):2820–2825

    CAS  PubMed  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  • Carneiro EM, Latorraca MQ, Araujo E, Beltra M, Oliveras MJ, Navarro M, Berna G, Bedoya FJ, Velloso LA, Soria B, Martin F (2009) Taurine supplementation modulates glucose homeostasis and islet function. J Nutr Biochem 20(7):503–511

    Article  CAS  PubMed  Google Scholar 

  • Cherif H, Reusens 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(2):341–348

    Article  CAS  PubMed  Google Scholar 

  • Cherif H, Reusens B, Dahri S, Remacle C, Hoet JJ (1996) Stimulatory effects of taurine on insulin secretion by fetal rat islets cultured in vitro. J Endocrinol 151(3):501–506

    Article  CAS  PubMed  Google Scholar 

  • Cnop M, Welsh N, Jonas JC, Jorns A, Lenzen S, Eizirik DL (2005) Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities. Diabetes 54(Suppl 2):S97–S107

    Article  CAS  PubMed  Google Scholar 

  • Colivicchi MA, Raimondi L, Bianchi L, Tipton KF, Pirisino R, Della Corte L (2004) Taurine prevents streptozotocin impairment of hormone-stimulated glucose uptake in rat adipocytes. Eur J Pharmacol 495(2–3):209–215

    Article  CAS  PubMed  Google Scholar 

  • Das J, Vasan V, Sil PC (2012) Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis. Toxicol Appl Pharmacol 258(2):296–308. doi:10.1016/j.taap.2011.11.009

    Article  CAS  PubMed  Google Scholar 

  • Eizirik DL, Moore F, Flamez D, Ortis F (2008) Use of a systems biology approach to understand pancreatic beta-cell death in Type 1 diabetes. Biochem Soc Trans 36(Pt 3):321–327. doi:10.1042/BST0360321

    Article  CAS  PubMed  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(5):1115–1119

    CAS  PubMed  Google Scholar 

  • Gomez Dumm CL, Console GM, Luna GC, Dardenne M, Goya RG (1995) Quantitative immunohistochemical changes in the endocrine pancreas of nonobese diabetic (NOD) mice. Pancreas 11(4):396–401

    Article  CAS  PubMed  Google Scholar 

  • Hennige AM, Burks DJ, Ozcan U, Kulkarni RN, Ye J, Park S, Schubert M, Fisher TL, Dow MA, Leshan R, Zakaria M, Mossa-Basha M, White MF (2003) Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes. J Clin Invest 112(10):1521–1532

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hostens K, Pavlovic D, Zambre Y, Ling Z, Van Schravendijk C, Eizirik DL, Pipeleers DG (1999) Exposure of human islets to cytokines can result in disproportionately elevated proinsulin release. J Clin Invest 104(1):67–72. doi:10.1172/JCI6438

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Inuwa IM, El Mardi AS (2005) Correlation between volume fraction and volume-weighted mean volume, and between total number and total mass of islets in post-weaning and young Wistar rats. J Anat 206(2):185–192

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Juntti-Berggren L, Larsson O, Rorsman P, Ammala C, Bokvist K, Wahlander K, Nicotera P, Dypbukt J, Orrenius S, Hallberg A et al (1993) Increased activity of L-type Ca2+ channels exposed to serum from patients with type I diabetes. Science 261(5117):86–90

    Article  CAS  PubMed  Google Scholar 

  • Kanayama A, Inoue J, Sugita-Konishi Y, Shimizu M, Miyamoto Y (2002) Oxidation of Ikappa Balpha at methionine 45 is one cause of taurine chloramine-induced inhibition of NF-kappa B activation. J Biol Chem 277(27):24049–24056. doi:10.1074/jbc.M110832200

    Article  CAS  PubMed  Google Scholar 

  • King AJ (2012) The use of animal models in diabetes research. Br J Pharmacol 166(3):877–894. doi:10.1111/j.1476-5381.2012.01911.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kornete M, Beauchemin H, Polychronakos C, Piccirillo CA (2013) Pancreatic islet cell phenotype and endocrine function throughout diabetes development in non-obese diabetic mice. Autoimmunity 46(4):259–268. doi:10.3109/08916934.2012.752462

    Article  CAS  PubMed  Google Scholar 

  • Lo SS, Hawa M, Beer SF, Pyke DA, Leslie RD (1992) Altered islet beta-cell function before the onset of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 35(3):277–282

    Article  CAS  PubMed  Google Scholar 

  • Marcinkiewicz J, Grabowska A, Bereta J, Bryniarski K, Nowak B (1998a) Taurine chloramine down-regulates the generation of murine neutrophil inflammatory mediators. Immunopharmacology 40(1):27–38

    Article  CAS  PubMed  Google Scholar 

  • Marcinkiewicz J, Grabowska A, Chain BM (1998b) Modulation of antigen-specific T-cell activation in vitro by taurine chloramine. Immunology 94(3):325–330

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marcinkiewicz J, Kontny E (2014) Taurine and inflammatory diseases. Amino Acids 46(1):7–20. doi:10.1007/s00726-012-1361-4

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Marcinkiewicz J, Nowak B, Grabowska A, Bobek M, Petrovska L, Chain B (1999) Regulation of murine dendritic cell functions in vitro by taurine chloramine, a major product of the neutrophil myeloperoxidase-halide system. Immunology 98(3):371–378

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Maturo J, Kulakowski EC (1988) Taurine binding to the purified insulin receptor. Biochem Pharmacol 37(19):3755–3760

    Article  CAS  PubMed  Google Scholar 

  • Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M (2000) Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes. Am J Clin Nutr 71(1):54–58

    CAS  PubMed  Google Scholar 

  • Nakhooda AF, Like AA, Chappel CI, Wei CN, Marliss EB (1978) The spontaneously diabetic Wistar rat (the “BB” rat). Studies prior to and during development of the overt syndrome. Diabetologia 14(3):199–207

    Article  CAS  PubMed  Google Scholar 

  • Nandhini AT, Thirunavukkarasu V, Anuradha CV (2005) Taurine modifies insulin signaling enzymes in the fructose-fed insulin resistant rats. Diabetes Metab 31(4 Pt 1):337–344

    Article  CAS  PubMed  Google Scholar 

  • Norquay LD, D’Aquino KE, Opare-Addo LM, Kuznetsova A, Haas M, Bluestone JA, White MF (2009) Insulin receptor substrate-2 in beta-cells decreases diabetes in nonobese diabetic mice. Endocrinology 150(10):4531–4540

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ohara-Imaizumi M, Cardozo AK, Kikuta T, Eizirik DL, Nagamatsu S (2004) The cytokine interleukin-1beta reduces the docking and fusion of insulin granules in pancreatic beta-cells, preferentially decreasing the first phase of exocytosis. J Biol Chem 279(40):41271–41274. doi:10.1074/jbc.C400360200

    Article  CAS  PubMed  Google Scholar 

  • Ortis F, Pirot P, Naamane N, Kreins AY, Rasschaert J, Moore F, Theatre E, Verhaeghe C, Magnusson NE, Chariot A, Orntoft TF, Eizirik DL (2008) Induction of nuclear factor-kappaB and its downstream genes by TNF-alpha and IL-1beta has a pro-apoptotic role in pancreatic beta cells. Diabetologia 51(7):1213–1225. doi:10.1007/s00125-008-0999-7

    Article  CAS  PubMed  Google Scholar 

  • Palmi M, Youmbi GT, Fusi F, Sgaragli GP, Dixon HB, Frosini M, Tipton KF (1999) Potentiation of mitochondrial Ca2+ sequestration by taurine. Biochem Pharmacol 58(7):1123–1131

    Article  CAS  PubMed  Google Scholar 

  • Reusens B, Sparre T, Kalbe L, Bouckenooghe T, Theys N, Kruhoffer M, Orntoft TF, Nerup J, Remacle C (2008) The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation. Diabetologia 51(5):836–845

    Article  CAS  PubMed  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(4):370–379

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro RA, Santos-Silva JC, Vettorazzi JF, Cotrim BB, Mobiolli DD, Boschero AC, Carneiro EM (2012) Taurine supplementation prevents morpho-physiological alterations in high-fat diet mice pancreatic beta-cells. Amino Acids 43(4):1791–1801. doi:10.1007/s00726-012-1263-5

    Article  CAS  PubMed  Google Scholar 

  • Ribeiro RA, Vanzela EC, Oliveira CA, Bonfleur ML, Boschero AC, Carneiro EM (2010) Taurine supplementation: involvement of cholinergic/phospholipase C and protein kinase A pathways in potentiation of insulin secretion and Ca2+ handling in mouse pancreatic islets. Br J Nutr 1–8

    Google Scholar 

  • Satoh H, Sperelakis N (1998) Review of some actions of taurine on ion channels of cardiac muscle cells and others. Gen Pharmacol 30(4):451–463

    Article  CAS  PubMed  Google Scholar 

  • Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87(2):91–99. doi:10.1139/Y08-110

    Article  CAS  PubMed  Google Scholar 

  • Sreenan S, Pick AJ, Levisetti M, Baldwin AC, Pugh W, Polonsky KS (1999) Increased beta-cell proliferation and reduced mass before diabetes onset in the nonobese diabetic mouse. Diabetes 48(5):989–996

    Article  CAS  PubMed  Google Scholar 

  • Tas S, Sarandol E, Ayvalik SZ, Serdar Z, Dirican M (2007) Vanadyl sulfate, taurine, and combined vanadyl sulfate and taurine treatments in diabetic rats: effects on the oxidative and antioxidative systems. Arch Med Res 38(3):276–283

    Article  CAS  PubMed  Google Scholar 

  • Teruya M, Takei S, Forrest LE, Grunewald A, Chan EK, Charles MA (1993) Pancreatic islet function in nondiabetic and diabetic BB rats. Diabetes 42(9):1310–1317

    Article  CAS  PubMed  Google Scholar 

  • Thomas HE, Kay TW (2000) Beta cell destruction in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse. Diabetes Metab Res Rev 16(4):251–261

    Article  CAS  PubMed  Google Scholar 

  • Tricarico D, Barbieri M, Camerino DC (2000) Taurine blocks ATP-sensitive potassium channels of rat skeletal muscle fibres interfering with the sulphonylurea receptor. Br J Pharmacol 130(4):827–834

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Trudeau JD, Dutz JP, Arany E, Hill DJ, Fieldus WE, Finegood DT (2000) Neonatal beta-cell apoptosis: a trigger for autoimmune diabetes? Diabetes 49(1):1–7

    Article  CAS  PubMed  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(7):3276–3284

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Bhattacharjee A, Fu J, Li M (1996) Abnormally expressed low-voltage-activated calcium channels in beta-cells from NOD mice and a related clonal cell line. Diabetes 45(12):1678–1683

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Bhattacharjee A, Zuo Z, Hu F, Honkanen RE, Berggren PO, Li M (1999) A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic beta-cell death. Endocrinology 140(3):1200–1204

    CAS  PubMed  Google Scholar 

  • Wei S, Huang Q, Li J, Liu Z, You H, Chen Y, Gong J (2012) Taurine attenuates liver injury by downregulating phosphorylated p38 MAPK of Kupffer cells in rats with severe acute pancreatitis. Inflammation 35(2):690–701. doi:10.1007/s10753-011-9362-0

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This study was supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); Fundação Carlos Chagas Filho de Amparo à Pesquisa (FAPERJ); Conselho Nacional para o Desenvolvimento Científico e Tecnológico (CNPq) and Instituto Nacional de Obesidade e Diabetes (CNPq/FAPESP). We thank Nicola Conran for editing English.

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Correspondence to Rosane Aparecida Ribeiro .

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Ribeiro, R.A., Santos-Silva, J.C., Vettorazzi, J.F., Cotrim, B.B., Boschero, A.C., Carneiro, E.M. (2015). Taurine Supplementation Enhances Insulin Secretion Without Altering Islet Morphology in Non-obese Diabetic Mice. In: Marcinkiewicz, J., Schaffer, S. (eds) Taurine 9. Advances in Experimental Medicine and Biology, vol 803. Springer, Cham. https://doi.org/10.1007/978-3-319-15126-7_27

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