Protective mechanism of glucose against alloxan-induced ${\beta}-cell$ damage: Pivotal role of ATP

Rho, Hye-Won;Lee, Ji-Na;Kim, Hyung-Rho;Park, Byung-Hyun;Park, Jin-Woo

  • Published : 2000.03.31

Abstract

Glucose prevents the development of diabetes induced by alloxan. In the present study, the protective mechanism of glucose against alloxan-induced ${\beta}-cell$ damage was investigated using HIT-T 15 cell, a Syrian hamster transformed ${\beta}-cell$ line. Alloxan caused ${\beta}-cell$ damages with DNA fragmentation, inhibition of glucose-stimulated insulin release, and decrease of cellular ATP level, but all of these ${\beta}-cell$ damages by alloxan were prevented by the presence of 20 mM glucose. Oligomycin, a specific inhibitor of ATP synthase, completely abolished the protective effects of glucose against alloxan-inudced cell damage. Furthermore, treatment of nuclei isolated from HIT-T15 cells with ATP significantly prevented the DNA fragmentation induced by $Ca^{2+}$. The results indicate that ATP produced during glucose metabolism plays a pivotal role in the protection of glucose against alloxan-induced ${\beta}-cell$ damage.

Keywords

References

  1. Diabetologia v.29 Insulin secretory responses of a clonal cell line of simian virus 40-transfected B cells Ashcroft, S.J.H.;Hammonds, P.;Harrison, D.E.
  2. J. Neurochemistry v.66 Assessment of the role of the glutathione and pentose phosphate pathways in the protection of primary cere-brocortical cultures from oxidative stress Ben-Yoseph, O.;Boxer, P.A.;Ross, B.D.
  3. Radiation Res. v.101 Poly(ADP-ribose) in the cellular response to DNA damage Berger, N.A.
  4. Science v.120 On the protection against alloxan diabetes by hexoses Bhattacharya, G.
  5. Endocrinology v.113 Uptake of labeled in mouse organs and mitochondria in vivo and in vitro Boquist, L.;Nelson, L.;Lorentzon, R.
  6. J. Biol. Chem. v.49 Generation of hydrogen peroxide, superoxide radical by 6-hydroxyl dopamine, dialuric acid and related agents Cohen, G.;Heikkila, R.E.
  7. J. Immunol. v.132 Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei lead to death Cohen, J.J.;Duke, R.C.
  8. J. Pharmacol. Exp. Ther. v.204 Effect of sulfhydryl binding reagents on islet tissue permeability: Protection and reversal by D-glucose and Phlorizin Cooperstein, S.J.;Watkins, D.
  9. Proc. Natl. Acad. Sci. USA v.80 Endogenous endonuclease-induced DNA fragmentation: An early event in cell-mediated cytolysis Duke, R.C.;Chervenak, R.;Cohen, J.J.
  10. Lancet v.I Necrosis of Langerhans produced experimentally Dunn, J.S.;Sheehan, H.L.;McLetchie, N.G.
  11. TIPS. v.6 Drugs and chemicals that produce diabetes Fischer, L.J.
  12. Diabetes v.37 Biosynthetic regulation of endogenous hamster insulin and exogenous rat insulin II intransfected HIT cells Gold, G.;Walker M.D.;Edwards, D.L.;Grodsky, G.M.
  13. Methods of Enzymol. v.1 Fractionation of cell components of animal tissues Hogeboom, G.H.
  14. Arch. Int. Pharmacodyn. v.293 The protective effect of glucose, but not 3-O-methyl glucose, against alloxan-induced diabetes depends upon the route of hexose administration Jansson, L.;Sandler, S.
  15. J. Biol. Chem. v.264 Calcium-activated DNA fragmentation in rat liver nuclei Jones, D.P.;McConkey, D.J.;Nicotera, P.;Orrenius, S.
  16. Biochim. Biophys. Acta v.1227 Role of $Ca^{2+}$ in alloxaninduced pancreatic ${\beta}$-cell damage Kim, H.R.;Rho, H.W.;Park, B.H.;Park, J.W.;Kim, J.S.;Kim, U.H.;Chung, M.Y.
  17. Kor. J. Biochemistry v.23 Protection of alloxan-induced ${\beta}$-cell damage of rat pancreas by $Ca^{2+}$-antagonists Kim, H.R.;Rho, H.W.;Park, J.W.;Kim, J.S.;Kim, U.H.;Jhee, E.C.
  18. Methods Enzymol. v.57 Determination of creatine kinase isoenzyme in human serum by an immunological method using purified firefly luciferase Ludin, A.
  19. Biochem. Pharmacol. v.31 Alloxan toxicity to the pancreatic B-cell. A new hypothesis Malaisse, W.J.
  20. Metabolism v.17 The effect of mannoheptulose on the phosphorylation of glucose and the secretion of insulin by islets of Langerhans Malaisse, W.J.;Lea, M.A.;Maiaisse-Lagae, F.
  21. BioEssay v.2 Molecular basis of experimental diabetes: Degeneration, Oncogenesis and regeneration of pancreatic B-cells of islet of Langerhans Okamoto, H.
  22. Biochem. Biophys. Res. Commun. v.210 Protective mechanism of glucose against alloxan-induced pancreatic ${\beta}$-cell damage Park, B.H.;Rho, H.W.;Park, J.W.;Cho, G.G.;Kim, J.S.;Chung, H.T.;Kim, H.R.
  23. Pharmacol. Rev. v.22 Drugs producing diabetes through damage of insulin secreting cells Rerup, C.C.
  24. J. Histochem v.31 Complementmediated cytolysis: A quick, simple method for determining levels of immunoglobulin E bound to mast cells Rosengard, B.R.;Cochrane, D.E.
  25. Proc. Natl. Acad. Sci. USA v.78 Insulin synthesis in a cloned cell line of simian virus 40-transformed hamster pancreatic beta cells Santerre, R.F.;Cook, R.A.;Crisel, R.M.D.;Sharp, J.D.;Schmidt, R.J.;Williams D.C.;Wilson, C.P.
  26. Diabetologia v.7 On the mechanism of glucose protection against alloxan toxicity Scheynius, A.;Taljedal, I.B.
  27. Indian J. Physiol. v.6 Protection against alloxan diabetes by glucose Sen, P.B.;Bhattacharya, G.
  28. Biochem. J. v.156 Stimulus-secretion coupling of glucose-induced insulin release. Does glycolysis control calcium transport in the B-cell? Sener, A.;Levy, J.;Malaisse, W.J.
  29. J. Biol. Chem. v.266 Alloxan-induced DNA strand breaks in pancreatic islets: Evidence for $H_2O_2$ as an intermediate Takasu, N.;Asawa, T.;Komiya, I.;Nagasawa, Y.;Yamada, T.
  30. J. Biol. Chem. v.257 Protection by superoxide dismutase, catalase, and poly(ADP-ribose) synthetase inhibitors against alloxan- and streptozotocin-induced islet DNA strand breaks and against inhibition of proinsulin synthesis Uchigata, Y.;Yamamoto, H.;Kawamura, A.;Okamoto, H.
  31. Endocrinology v.102 Alloxan uptake by isolated rat islets of Langerhans Weaver, D.C.;McDaniel, M.L.;Lacy, P.E.
  32. Biochem. Biophys. Res. Commun. v.103 DNA strand breaks in pancreatic islets by in vivo administration of alloxan or streptozotocin Yamamoto, H.;Uchigata, Y.;Okamoto, H.
  33. Am. J. Physiol. v.224 Glucose and alloxan interactions in the pancreatic islets Zawalich, W.S.;Beidler, L.M.