Abstract
Metallothionein (MT) concentrations were determined in the cytosol of isolated pancreatic islets of mice, using both the cadmium (Cd)-heme and the Cd-Chelex assay. Both constitutive MT levels and significant MT induction were detected in islet cells. For MT induction, mice were injected intraperitoneally (i.p.) with either zinc sulfate (Zn) or the diabetogen streptozotocin (STZ). Following an i.p. injection of 15 mg Zn-kg−1 body weight (body wt), the mean index of MT induction found in islets was comparable to that found in liver tissue, which was used as control. After i.p. injection of 30 mg Zn-kg−1 or a single high dose of STZ (100 or 200 mg·kg−1), the indices of MT induction in islets exceeded those in liver by a factor of 1.3, 2.5, or 1.5. After multiple low doses of STZ (3 or 5 x 40 mg·kg−1 given on consecutive days), in contrast, the MT induction indices in islets exceeded those in liver by a factor of 3.5 and 3.9 for 3×40 respectively 5×40 mg STZ· kg−1. In conclusion, our results demonstrate constitutive MT levels in isolated pancreatic islets and significant MT induction after i. p. injection with Zn or STZ, in particular after repeated low doses of STZ.
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References
Abel J, de Ruiter N (1989) Inhibition of hydroxyl-radical-generated DNA degradation by metallothionein. Toxicol Lett 64: 177–180
Bartsch R, Klein D, Summer KH (1990) The Cd-Chelex assay: a new sensitive method to determine metallothionein containing zinc and cadmium. Arch Toxicol 64: 177–180
Baumann JW, Lin J, Lin YP, Klaassen CD (1991) Increase in metallothionein produced by chemicals that induce oxidative stress. Toxicol Appl Pharmacol 110: 347–354
Boquist L, Lernmark A (1969) Effects on the endocrine pancreas in Chinese hamsters fed zinc deficient diets. Acta Pathol Microbiol Scand 76: 215–228
DiSivestro RA, Cousins RJ (1984) Glucocorticoid independent mediation of interleukin-1 induced changes in serum zinc and metallothionein levels. Life Sci 35: 2113–2118
Dunn MA, Blalock TL, Cousins RJ (1987) Metallothionein. Proc Exp Biol Med 185: 107–119
Failla ML, Cousins RJ (1978) Zinc uptake by isolated rat liver parenchymal cells. Biochem Biophys Acta 538: 435–444
Frank BH, Veros AJ (1968) Physical studies on proinsulin: association behavior and confirmation in solution. Biochem Biophys Res Commun 32: 155–160
Friedmann RL, Manly SP, McMahon M, Kerr IM, Stark GR (1984) Transcriptional and post-transcriptional regulation of interferoninduced gene expression in human cells. Cell 38: 745–755
Gotoh M, Maki T, Kiyoizumi T, Satomi S, Monaco AP (1985) An improved method for isolation of mouse pancreatic islets. Transplantation 40: 437–438
Hager LJ, Palmiter RD (1981) Transcriptional regulation of mouse liver metallothionein-I gene by glucocorticoids. Nature 291: 340–342
Hamer DH (1986) Metallothionein. Annu Rev Biochem 55: 913–951
Kägi JHR, Kojima Y (eds) (1987) Metallothionein II. Birkhäuser Verlag, Basel
Karin M, Imbra RJ, Heguy A, Wong G (1985) Interleukin 1 regulates metallothionein gene expression. Mol Cell Biol 5: 2866–2869
Klinkhammer C, Popowa P, Gleichmann H (1988) Specific immunity to streptozotocin: cellular requirements for induction of lymphoproliferation. Diabetes 37: 74–80
Lacy PE, Kostianovsky M (1967) Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16: 35
Lowry OM, Rosebrough NJ, Farr Al, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Oh SH, Deagen JT, Whanger PD, Weswig PH (1978) Biological function of metallothionein. V. Its induction in rats by various stresses. Am J Physiol 234: 282–285
Onosaka S, Min KS, Fujita Y, Tanaka K, Iguchi S, Okada Y (1988) High concentration of pancreatic metallothionein in normal mice. Toxicology 50: 27–35
Piscator M (1964) Om kadmium i normala människonjurar samt redogörelse för isolering av metallothionein ur lever fran kadmiumexponerade kaniner. Nord Hyg Tidskr 45: 76–82
Quaterman J, Mills CF, Humphries WR (1966) The reduced secretion of and sensitivity to insulin in zinc-deficient rats. Biochem Biophys Res Commun 25: 354–358
Robinson LK, Hurley LS (1981) Effect of maternal zinc deficiency food restriction on fetal pancreas. 2. Insulin and glucagon. J Nutr 111: 869–877
Takasu N, Komiya I, Asawa T, Nagasawa Y, Yamada T (1991) Streptozotocin- and alloxan-induced H2O2 generation and DNA fragmentation in pancreatic islets. Diabetes 40: 1141–1145
Thornalley PJ, Vasak M (1985) Possible role for metallothionein in protection against radiation-induced oxidative stress. Kinetics and mechanism of its reaction with Superoxide and hydroxyl radicals. Biochem Biophys Acta 827: 36–44
Wilson GL, Leiter EH (1990) Streptozotocin interactions with pancreatic β cells and the induction of insulin-dependent diabetes. In: Dyrberg T (ed) Curr Top Microbiol Immunol. Springer Verlag, Berlin, Heidelberg, pp 27–54
Winge DR, Miklossy KA (1982) Domain nature of metallothionein. J Biol Chem 257: 3471–3476
Yamamoto H, Uchigata Y, Okamoto H (1981) Streptozotocin and alloxan induce DNA breaks and poly (ADP-ribose) synthetase in pancreatic islets. Nature 294: 284–286
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Part of this work are included in the doctoral theses of S. Z. and F. G.
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Zimny, S., Gogolin, F., Abel, J. et al. Metallothionein in isolated pancreatic islets of mice: Induction by zinc and streptozotocin, a naturally occurring diabetogen. Arch Toxicol 67, 61–65 (1993). https://doi.org/10.1007/BF02072037
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DOI: https://doi.org/10.1007/BF02072037