Advertisement

Diabetology International

, Volume 9, Issue 4, pp 234–242 | Cite as

Taurine improves glucose tolerance in STZ-induced insulin-deficient diabetic mice

  • Yuko Nakatsuru
  • Yuko Murase-Mishiba
  • Megumi Bessho-Tachibana
  • Jungo Terasaki
  • Toshiaki Hanafusa
  • Akihisa Imagawa
Original Article
  • 124 Downloads

Abstract

Blood glucose levels fluctuate considerably in diabetic patients with reduced secretion of endogenous insulin. We previously reported that glucagon is secreted excessively in these patients and that taurine increases glucagon secretion in vitro. Therefore, we hypothesized that glucose tolerance would further deteriorate when taurine was administered to diabetic mice incapable of insulin secretion. We generated four groups of streptozotocin (STZ)-treated C57BL/6J mice (STZ-mice): STZ-mice without taurine treatment (STZ-Con), STZ-mice treated with 0.5% (w/v) taurine (STZ-0.5% Tau), STZ-mice treated with 1% (w/v) taurine (STZ-1% Tau), and STZ-mice treated with 2% (w/v) taurine (STZ-2% Tau). Mice were treated for 4 weeks, and then, we evaluated glucose tolerance, pancreatic β-cell area and α-cell area, pancreatic insulin and glucagon content, and daily blood glucose variability. As a result, following the administration of taurine, glucose tolerance improved, both pancreatic β- and α-cell area increased, and both insulin and glucagon content increased. In the 1% taurine administration group, blood glucose variability decreased. These unexpected results suggest that taurine improves glucose tolerance, in spite of its subsequent increased glucagon production, partly by increasing pancreatic β-cells and insulin production in vivo.

Keywords

Insulin-dependent diabetes Taurine Glucagon Glucose variability 

Notes

Acknowledgements

This study was supported by a Grant-in-aid (25461367) from the Ministry of Science, Education and Culture of Japan (to Y.M–M.).

Compliance with ethical standards

Animal rights

All institutional and national guidelines for the care and use of laboratory animals were followed.

Conflict of interest

TH. has received honoraria from Novo Nordisk Pharma for lectures. A.I. has received honoraria from Eli Lilly Japan for lectures. Y.N., Y.M–M., M.B-T., and J.T. declare that they have no conflict of interest.

References

  1. 1.
    American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Supplement 1):S11–24.CrossRefGoogle Scholar
  2. 2.
    Bessho M, Murase-Mishiba Y, Tsutsumi C, Haseda F, Imagawa A, Terasaki J, Hanafusa T. Glycaemic instability correlates with a hyperglucagonaemic response in patients with type 1 diabetes without residual beta-cell function. Diabetes Res Clin Pract. 2013;102(2):e38–40.CrossRefGoogle Scholar
  3. 3.
    Zhang Q, Ramracheya R, Lahmann C, Tarasov A, Bengtsson M, Braha O, Braun M, Brereton M, Collins S, Galvanovskis J, Gonzalez A, Groschner LN, Rorsman NJ, Salehi A, Travers ME, Walker JN, Gloyn AL, Gribble F, Johnson PR, Reimann F, Ashcroft FM, Rorsman P. Role of KATP channels in glucose-regulated glucagon secretion and impaired counter regulation in type 2 diabetes. Cell Metab. 2013;18(6):871–82.CrossRefGoogle Scholar
  4. 4.
    Diao J, Asghar Z, Chan CB, Wheeler MB. Glucose-regulated glucagon secretion requires insulin receptor expression in pancreatic alpha-cells. J Biol Chem. 2005;280(39):33487–96.CrossRefGoogle Scholar
  5. 5.
    Kawamori D, Kurpad AJ, Hu J, Liew CW, Shih JL, Ford EL, Herrera PL, Polonsky KS, McGuinness OP, Kulkarni RN. Insulin signaling in alpha cells modulates glucagon secretion in vivo. Cell Metab. 2009;9(4):350–61.CrossRefGoogle Scholar
  6. 6.
    Bessho M, Murase-Mishiba Y, Imagawa A, Terasaki J, Hanafusa T. Possible contribution of taurine to distorted glucagon secretion in intra-islet insulin deficiency: a metabolome analysis using a novel α-cell model of insulin-deficient diabetes. PLoS One. 2014;9(11):e113254.CrossRefGoogle Scholar
  7. 7.
    Weiss SJ, Klein R, Slivka A, Wei M. Chlorination of taurine by human neutrophils. Evidence for hypochlorous acid generation. J Clin Invest. 1982;70(3):598–607.CrossRefGoogle Scholar
  8. 8.
    Gürer H, Ozgünes H, Saygin E, Ercal N. Antioxidant effect of taurine against lead-induced oxidative stress. Arch Environ Contam Toxicol. 2001;41(4):397–402.CrossRefGoogle Scholar
  9. 9.
    Marcinkiewicz J, Kontny E. Taurine and inflammatory diseases. Amino Acids. 2014;46(1):7–20.CrossRefGoogle Scholar
  10. 10.
    Kontny E, Szczepańska K, Kowalczewski J, Kurowska M, Janicka I, Marcinkiewicz J, Maśliński W. The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid arthritis fibroblast-like synoviocytes. Arthritis Rheum. 2000;43(10):2169–77.CrossRefGoogle Scholar
  11. 11.
    Franconi F, Loizzo A, Ghirlanda G, Seghieri G. Taurine supplementation and diabetes mellitus. Curr Opin Clin Nutr Metab Care. 2006;9(1):32–6.CrossRefGoogle Scholar
  12. 12.
    Tokunaga H, Yoneda Y, Kuriyama K. Streptozotocin-induced elevation of pancreatic taurine content and suppressive effect of taurine on insulin secretion. Eur J Pharmacol. 1983;87(2–3):237–43.CrossRefGoogle Scholar
  13. 13.
    Alvarado-Vásquez N, Zamudio P, Cerón E, Vanda B, Zenteno E, Carvajal-Sandoval G. Effect of glycine in streptozotocin-induced diabetic rats. Comp Biochem Physiol C Toxicol Pharmacol. 2003;134(4):521–7.CrossRefGoogle Scholar
  14. 14.
    Tenner TE Jr, Zhang XJ, Lombardini JB. Hypoglycemic effects of taurine in the alloxan-treated rabbit, a model for type 1 diabetes. Adv Exp Med Biol. 2003;526:97–104.CrossRefGoogle Scholar
  15. 15.
    Arany E, Strutt B, Romanus P, Remacle C, Reusens B, Hill DJ. Taurine supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice. Diabetologia. 2004;47(10):1831–7.CrossRefGoogle Scholar
  16. 16.
    Winiarska K, Szymanski K, Gorniak P, Dudziak M, Bryla J. Hypoglycaemic, antioxidative and nephroprotective effects of taurine in alloxan diabetic rabbits. Biochimie. 2009;91(2):261–70.CrossRefGoogle Scholar
  17. 17.
    Chang KJ, Kwon W. Immunohistochemical localization of insulin in pancreatic beta-cells of taurine-supplemented or taurine-depleted diabetic rats. Adv Exp Med Biol. 2000;483:579–87.CrossRefGoogle Scholar
  18. 18.
    Gavrovskaya LK, Ryzhova OV, Safonova AF, Matveev AK, Sapronov NS. Protective effect of taurine on rats with experimental insulin-dependent diabetes mellitus. Bull Exp Biol Med. 2008;146(2):226–8.CrossRefGoogle Scholar
  19. 19.
    O’Brien BA, Harmon BV, Cameron DP, Allan DJ. Beta-cell apoptosis is responsible for the development of IDDM in the multiple low-dose streptozotocin model. J Pathol. 1996;178(2):176–81.CrossRefGoogle Scholar
  20. 20.
    Serrrvice FJ, Molnar GD, Rosevear JW, Ackerman E, Gatewood LC, Taylor WF. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970;19(9):644–55.CrossRefGoogle Scholar
  21. 21.
    Tokunaga H, Yoneda Y, Kuriyama K. Protective actions of taurine against streptozotocin-induced hyperglycemia. Biochem Pharmacol. 1979;28(18):2807–11.CrossRefGoogle Scholar
  22. 22.
    Talchai C, Xuan S, Lin HV, Sussel L, Accili D. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell. 2012;150(6):1223–34.CrossRefGoogle Scholar
  23. 23.
    Fernandes A, King LC, Guz Y, Stein R, Wright CV, Teitelman G. Differentiation of new insulin-producing cells is induced by injury in adult pancreatic islets. Endocrinology. 1997;138(4):1750–62.CrossRefGoogle Scholar
  24. 24.
    Guz Y, Nasir I, Teitelman G. Regeneration of pancreatic beta cells from intra-islet precursor cells in an experimental model of diabetes. Endocrinology. 2001;142(11):4956–68.CrossRefGoogle Scholar
  25. 25.
    Thorel F, Népote V, Avril I, Kohno K, Desgraz R, Chera S, Herrera PL. Conversion of adult pancreatic alpha-cells to beta-cells after extreme beta-cell loss. Nature. 2010;464(7292):1149–54.CrossRefGoogle Scholar
  26. 26.
    Hernández-Benítez R, Ramos-Mandujano G, Pasantes-Morales H. Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Res. 2012;9(1):24–34.CrossRefGoogle Scholar
  27. 27.
    Osakada F, Jin ZB, Hirami Y, Ikeda H, Danjyo T, Watanabe K, Sasai Y, Takahashi M. In vitro differentiation of retinal cells from human pluripotent stem cells by small-molecule induction. J Cell Sci. 2009;122(Pt 17):3169–79.CrossRefGoogle Scholar
  28. 28.
    Ramos-Mandujano G, Hernández-Benítez R, Pasantes-Morales H. Multiple mechanisms mediate the taurine-induced proliferation of neural stem/progenitor cells from the subventricular zone of the adult mouse. Stem Cell Res. 2014;12(3):690–702.CrossRefGoogle Scholar
  29. 29.
    Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42(6):2223–32.CrossRefGoogle Scholar
  30. 30.
    Kim J, Wong PK. Loss of ATM impairs proliferation of neural stem cells through oxidative stress-mediated p38 MAPK signaling. Stem Cells. 2009;27(8):1987–98.CrossRefGoogle Scholar
  31. 31.
    Sharma RK, Zhou Q, Netland PA. Effect of oxidative preconditioning on neural progenitor cells. Brain Res. 2008;1243:19–26.CrossRefGoogle Scholar
  32. 32.
    Trachtman H, Futterweit S, Sturman JA. Cerebral taurine transport is increased during streptozocin-induced diabetes in rats. Diabetes. 1992;41(9):1130–40.CrossRefGoogle Scholar

Copyright information

© The Japan Diabetes Society 2018

Authors and Affiliations

  • Yuko Nakatsuru
    • 1
  • Yuko Murase-Mishiba
    • 1
  • Megumi Bessho-Tachibana
    • 1
  • Jungo Terasaki
    • 1
  • Toshiaki Hanafusa
    • 1
  • Akihisa Imagawa
    • 1
  1. 1.Department of Internal Medicine (I)Osaka Medical CollegeTakatsukiJapan

Personalised recommendations