Summary
Pancreatic islets, newly formed in vitro were incubated in the presence of streptozotocin (STZ; 0.4 mM) for up to 6 h. Ultrastructural changes first appeared between 2 and 4 h; heterochromatization, was followed by swelling of nuclear and reticular membranes, vesiculation of the Golgi apparatus, fragmentation of cell membranes and finally mitochondrial destruction. At the end of the experiment all the B cells were destroyed, whereas the other cell types remained intact. Exogenous ZnSO4 was added during preincubation periods to increase the intrainsular zinc content and to determine any protective effect against STZ-cytotoxicity. Since the addition of zinc had no obvious effect, it is suggested that STZ cytotoxicity on B cells cannot be attributed to competition for zinc between copper-zinc Superoxide dismutase (Cu-Zn-SOD) and the crystallization of insulin.
Similar content being viewed by others
References
Asayama K, English D, Slonim AE, Burr IM (1984) Chemilu- minescence as an index of drug-induced free radical. Dia- betes 33:160–162
Bonner-Weir S, Trent DF, Honey RN, Weir GC (1981) Re- sponses of neonatal rat islet to streptozotocin, limited B-cell regeneration and hyperglycemia. Diabetes 30:64–69
Boquist L, Lorentzon R (1979) Stereological study of endoplas- mic reticulum, Golgi complex and secretory granules in the B-cells of normal and alloxan treated mice. Virchows Arch [Cell Pathol] 31:235–241
Chang Y, Diani AR (1985) Chemically and hormonally induced diabetes mellitus. In: Volk BW, Arquilla ER (eds) The dia- betic pancreas. Plenum Press, New York London, pp 415–431
Crouch RK, Gandy SE, Kimsey G, Galbraith RA, Galbraith GMP, Buse MG (1981) The inhibition of islet Superoxide dismutase by diabetogenic drugs. Diabetes 30:235–241
Falkmer S, Odselius R, Blondel B, Prentki M, Wollheim CB (1985) Energy dispersive X-ray microanalysis of zinc and calcium in organelles of insulin-producing cells of the mouse, rat and a fish. Biomed Biochem Acta 44:37–43
Figlewicz DP, Formby B, Hodgson AT, Schmid FG, Grodsky GM (1980) Kinetics of 65Zn uptake and distribution from cultured rat islets of Langerhans. Diabetes 29:767–773
Fridovich I (1975) Superoxide dismutase. Ann Rev Biochem 44:147–159
Ganda OP, Rossini AA, Like AA (1976) Studies of streptozoto- cin diabetes. Diabetes 25:595–603
Gandy SE, Buse MG, Crouch RK (1982) Protective role of Superoxide dismutase against diabetogenic drugs. Am Soc Clin Inv 70:650–658
Ghafghazi T, McDaniel ML, Lacy PE (1981) Zinc-induced inhi- bition of insulin secretion from isolated rat islets of Langer- hans. Diabetes 30:341–345
Gold G, Manning M, Heldt A, Nowlain R, Petit JR, Gordsky GM (1981) Diabetes induced with multiple subdiabetogenic doses of streptozotocin. Lack of protection by exogenous Superoxide dismutase. Diabetes 30:634–638
Grankvist K, Marklund S, Sehlin J, Täljedal IB (1979) Superox- ide dismutase, catalase and scavengers of hydroxyl radical protect against the toxic action of alloxan on pancreatic islet cells in vitro. Biochem J 182:17–25
Grankvist K, Marklund SL, Taljedal IB (1981) Cu-Zn superox- ide dismutase, Mn Superoxide dismutase, catalase and glu- tathione peroxidase in pancratic islets and other tissues in the mouse. Biochem J 199:393–398
Heal JM, Fox PA, Schein PS (1979) Effect of carbamoylation on the repair of nitrosourea-induced DNA alkylation dam- age in L 1210 cells. Cancer Res 39:82–89
Hellerström C, Lewis NJ, Borg H, Johnson R, Freinkel N (1979) Method for large-scale isolation of pancreatic islets by tissue culture of fetal rat pancreas. Diabetes 28:769–776
Like AA, Rossini AA (1976) Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193:415–417
Like AA, Appel MC, Williams RM, Rossini AA (1978) Strepto- zotocin-induced pancreatic insulitis in mice. Morphologic and physiologic studies. Lab Invest 38:470–485
Lorentzon R, Boquist L (1979) Stereological study of B-cell mitochondria in alloxan-treated mice. Virchows Arch [Cell Pathol] 31:227–233
Malaisse WJ (1982) Commentary: Alloxan toxicity to the pan- creatic B-cell, a new hypothesis. Biochem Pharmacol 31:3527–3534
Masquelier D, Amory B, Mourmeaux JL, Remacle C (1986) Cell interactions during the in vitro neoformation of fetal pancreatic islets. Cell Differ 18:199–211
Michel C, Chariot J, Souchard M, Roze C (1986) Modifications of the endocrine pancreas in rats after mixed endocrine- exocrine destruction by streptozotocin and ethionine with a protein-free diet. Cell Mol Biol 32:41–54
Mourmeaux JL, Remacle C, Henquin JC (1985) Morphological and functional characteristics of islets neoformed during tis- sue culture of fetal rat pancreas. Molec Cell Endocrinol 39:237–246
Okamoto H (1985) Molecular basis of experimental diabetes: degeneration, oncogenis and regeneration of pancreatic B- cells of islets of Langerhans. Bio Essays 2:15–21
Papaccio G, Pisanti FA, Frascatore S (1986) Acetyl-homocys- teine-thiolactone-induced increase of Superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozo- tocin. Diabetes 35:470–474
Remacle C, De Clercq L, Delaére P, Many MC, Gommers A (1980) Organ culture of the islet of Langerhans from young and senescent rats. Cell Tissue Res 207:429–448
Rerup C, Tarding F (1969) Streptozotocin and alloxan diabetes in mice. Eur J Pharmacol 7:89–96
Robbins J, Sharp RA, Slonim AE, Burr IM (1980) Protection against streptozotocin-induced diabetes by Superoxide dis- mutase. Diabetologia 18:55–58
Sandler S, Swenne I (1983) Streptozotocin, but not alloxan, induces DNA repair synthesis in mouse pancreatic islets in vitro. Diabetologia 25:444–447
Weaver DC, McDaniel ML, Lacy PE (1978) Alloxan uptake by isolated rat islets of Langerhans. Endocrinology 102:1847–1855
Yamamoto H, Uchigata Y, Okamoto H (1981) Streptozotocin and alloxan induce DNA strand breaks and poly(ADP-ri- bose) synthetase in pancreatic islets. Nature (Lond) 294:284–286
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Flament, P., Remacle, C. Ultrastructural aspects of streptozotocin cytotoxicity on rat pancreatic islets in vitro. Virchows Archiv B Cell Pathol 53, 107–112 (1987). https://doi.org/10.1007/BF02890232
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF02890232