Summary
Methylene blue (an oxidant of NADPH), diamide (an oxidant of glutathion-SH [GSH]) and tertbutyl hydroperoxide (a substrate of glutathione peroxidase) significantly decreased the GSH content of pancreatic rat islets and decreased their GSH/GSSG ratio. They also significantly depressed the single peak insulin response to tolbutamide by the isolated perfused pancreas as well as its synergistic action with glucose in isolated pancreatic islets.
These results suggest that the effect of tolbutamide alone and its synergistic action with glucose could depend on the islet NADPH and GSH. In addition it appears that augmentation of tolbutamide action by glucose in insulin release is mediated by the provision of additional NADPH and GSH through glucose metabolism.
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Ammon, H. P. T.: Effect of glucose and methylene blue on NADP, NADPH and insulin secretion of isolated pancreatic rat islets. Naunyn-Schmiedeberg's Arch. Pharmacol. 277, R1 (1973)
Ammon, H. P. T.: Effect of tolbutamide on aminophylline, 3,5-AMP-dibutyrate-or glucagon-induced insulin release from pancreatic islets after impairment of pyridine nucleotide metabolism caused by 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 251–264 (1975)
Ammon, H. P. T., Akhtar, M. S., Niklas, H., Hegner, D.: Inhibition of p-chloromercuribenzoate- and glucose-induced insulin release in vitro by methylene blue, diamide and tert-butyl hydroperoxide. Mol. Pharmacol. 13, 598–605 (1977)
Ammon, H. P. T., Grimm, A., Wagner-Teschner, D., Verspohl, E. J., Händel, M.: GSH/GSSG and NADPH/NADP ratios of pancreatic islets depend on glucose concentration. Diabetes 27, Suppl. 2, 466 (1978)
Ashcroft, S. J. H., Weerasinghe, L. C. C., Basset, J. M., Randle, P. J.: The pentose phosphate cycle and insulin release in mouse pancreatic islets. Biochem. J. 126, 525–532 (1972)
Bowen, V., Lazarus, N. R.: Insulin release from the perfused rat pancreas. Mode of action of tolbutamide. Biochem. J. 142, 385–389 (1974)
Curry, D. L., Bennett, L. L., Grodsky, G. M.: Dynamics of insulin secretion by the perfused rat pancreas. Endocrinology 83, 572–584 (1968)
Hellman, B., Täljedal, I.-B.: Effects of sulfonylureas derivatives on pancreatic β-cells. In: Handb. Exp. Pharm., Vol. 32/2 (G. V. R. Born, O. Eichler, A. Farah, H. Herken, and A. D. Welch, eds.), pp. 175–194. Berlin, Heidelberg, New York: Springer 1975
Hellman, B., Sehlin, J., Täljedal, I.-B.: The pancreatic β-cell recognition of insulin secretagogues. II. Site of action of tolbutamide. Biochem. Biophys. Res. Commun. 45, 1384–1388 (1971)
Hellman, B., Sehlin, J., Täljedal, I.-B.: The pancreatic β-cell recognition of insulin secretagogues. IV. Uptake of sulfonylureas by islet tissue. Diabetologia 9, 210–216 (1973)
Hellmann, B., Lernmark, A., Sehlin, J., Söderberg, M., Täljedal, I.-B.: On the possible role of thiol groups in the insulin releasing action of mercurials, organic disulfides, alkylating agents, and sulfonylureas. Endocrinology 99, 1398–1406 (1976)
Hissin, P. J., Hilf, R.: A fluorimetric method for determination of oxidized and reduced glutathione in tissues. Anal. Biochem. 74, 214–226 (1976)
Kosower, N. S., Kosower, E. M., Wertheim, B., Correa, W.: Diamide, a new reagent for the intracellular oxidation of glutathione to the disulfide. Biochem. Biophys. Res. Commun. 37, 593–596 (1969)
Kosower, E. M., Correa, W., Kinon, B. J., Kosower, N. S.: Glutathione. VII. Differentiation among substrates by the thiol oxidizing agent diamide. Biochim. Biophys. Acta 264, 39–44 (1972)
Lacy, P. E., Kostianovsky, M.: Method for isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35–39 (1967)
Landgraf, R., Kotler-Brajtburg, J., Matschinsky, F. M.: Kinetics of insulin release from the perfused rat pancreas caused by glucose, glucosamine and galactose. Proc. Nat. Acad. Sci. U.S.A. 68, 536–540 (1971)
Owens, C. W. I., Belcher, R. V.: A colorimetric micro-method for the determination of glutathione. Biochem. J. 94, 705–711 (1965)
Panten, U.: Biochemical events in pancreatic islets as caused by sulfonylurea derivates. In: Pharmacology and the future of man. Congr. Pharmacol. San Francisco, Vol. 3, pp. 214–220 Basel: Karger 1972.
Sass, M. D., Caruso, C. J., Axelrod, D. R.: Mechanism of the TPNH-linked reduction of methemoglobin by methylene blue. Clin. Chim. Acta 24, 77–85 (1969)
Sies, H., Gerstenecker, C., Menzel, H., Flohé, L.: Oxidation in the NADP system and release of GSSG from hemoglobin-free perfused rat liver during peroxidatic oxidation of glutathione by hydroperoxides. FEBS Lett. 27, 171–175 (1972)
Soeldner, J. S., Slone, D.: Critical variables in the radioimmunoassay of serum insulin using the double antibody technique. Diabetes 14, 771–779 (1965)
Srivastava, S. K., Awashti, Y. C., Beutler, E.: Useful agents for the study of glutathione metabolism in erythrocytes — Organic hydroperoxides. Biochem. J. 139, 289–295 (1974)
Tietze, F.: Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal. Biochem. 27, 502–522 (1966)
Widström, A., Cerasi, E.: Modulation of glucose induced insulin release by tolbutamide in man. Acta Endocrinol. (Kbh.) 72, 519–531 (1973)
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Ammon, H.P.T., Akhtar, M.S., Grimm, A. et al. Effect of methylene blue and thiol oxidants on pancreatic islet GSH/GSSG ratios and tolbutamide mediated insulin release in vitro. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 91–96 (1979). https://doi.org/10.1007/BF00506556
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DOI: https://doi.org/10.1007/BF00506556