Summary
Alloxan 5 mM depolarised the islet but not the acinar cells of mouse pancreatic segmentsin vitro. This effect was prevented by D-glucose but not by glutathione, 3, 0, methyl-α-D-glucose, D-glucosamine, D-mannoheptulose, or L-leucine. Pretreatment of islet β-cells with streptozotocin 20 mM caused no depolarization but inhibited the generation of action potentials by D-glucose, L-leucine, D-mannose and D-glyceraldehyde, whereas tolbutamide-induced action potentials were not blocked; the alkylating moiety of streptozotocin, N-nitroso N- methyl urea produced similar effects. Prior exposure of the islet cells to nicotinamide 4.1 mM conferred protection against streptozotocin action. These observations are discussed in relation to the diabetogenic action of alloxan and streptozotocin.
Résumé
L'alloxane (5 mM) a dépolarisé les cellules des îlots, mais non les cellules de l'acinus des segments pancréatiques chez la sourisin vitro. Cet effet était anihilé par le D-glucose, mais non par le glutathion, le3, 0, méthyl-α-D-glucose, la D-glucosamine, le D-mannoheptulose ou la L-leucine. Le pré-traitement des cellules ß des îlots à la streptozotocine (20 mM) n'a pas provoqué de dépolarisation, mais a inhibé la génération de potentiels d'action par le D-glucose, la L'leucine, le D-mannose et la D-glycéraldéhyde, tandis que les potentiels d'action provoqués par la tolbutamide n'étaient pas bloqués; la partie alkylante de la streptozotocine, la N-nitroso-N-méthyl urée produisaient les mêmes effets. L'exposition préalable des cellules des îlots à l'amide nicotinique (4.1 mM) fournissait une protection contre l'action de la streptozotocine. Ces observations sont discutées en relation avec l'action diabétogène de l'alloxane et de la streptozotocine.
Zusammenfassung
5 mM Alloxan depolarisiert die Inseln aber nicht die Azinuszellen von Segmenten des Mäusepankreasin vitro. Diese Wirkung konnte durch D-Glucose aber nicht durch Glutathion, 3, 0, methyl-α-D-Glucose, D-Glucosamin, D-Mannoheptulose, oder L-Leucin verhindert werden. Die Vorbehandlung vonβ-Zellen der Inseln mit 20 mM Streptozotocin verursachte keine Depolarisierung aber verhinderte die Erzeugung von Aktionspotentialen durch D-Glucose, L-Leucin, D-Mannose und D-Glyceraldehyden, während durch Tolbutamid induzierte Aktionspotentiale nicht blockiert wurden. Der alkylierende Teil von Streptozotocin, der N-nitroso-N-methyl-Harnstoff zeigte ähnliche Wirkungen. Ein vorheriger Kontakt der Inselzellen mit Nicotinamid 4,1 mM erzeugte einen Schutz gegenüber der Streptozotocinwirkung. Diese Beobachtungen werden in Verbindung mit der diabetogenen Wirkung von Alloxan und Streptozotocin diskutiert.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bhattacharya, G.: Protection against alloxan diabetes by mannose and fructose. Science117, 230–231 (1953).
—: On the protection of alloxan diabetes by hexoses. Science120, 841–843 (1954).
Brosky, G., Logothetopoulos, J.: Streptozotocin diabetes in the mouse and guinea-pig. Diabetes18, 606–611 (1969).
Dean, P.M., Matthews, E.K.: Alloxan on islet cell membrane potentials. Brit. J. Pharmac.34, 677 (1968).
— —: Glucose-induced electrical activity in pancreatic islet cells. J. Physiol.210, 255–264 (1970a).
— —: Electrical activity in pancreatic islet cells: effect of ions. J. Physiol.210, 255–275 (1970b).
- - The effect of some metabolic intermediates on islet cell membrane potentials. Biochem. biophys. Acta (1971) in the press.
Garnet, E.R.: Prediction of stability in pharmaceutical preparations. 7. The solution degradation of the antibiotic streptozotocin. J. Amer. Pharm. Assoc.47, 767–777 (1960).
Golden, P., Baird, L., Malaisse, W.J., Malaisse-Lagae, F., Walker, M.: Effect of streptozotooin on glucose-induced insulin secretion by isolated islets of Langerhans. Diabetes20, 513–518 (1971).
Hammarstrom, L., Hellman, B., Ullberg, S.: On the accumulation of alloxan in the pancreatic β-cells. Diabetologia2, 340–345 (1966).
Lazarow, A.: Protective effect of glutathione and cysteine against alloxan diabetes in the rat. Proc. Soc. exp. Biol. Med.61, 441–447 (1946).
Magee, P.N., Shoental, R.: Carcinogenesis by nitroso compounds. Brit. Med. Bull.20, 102–106 (1964).
Mansford, K.R.L., Opie, L.: Comparison of metabolic abnormalities in diabetes mellitus induced by streptozotooin or by alloxan. Lancet1968, 670–671.
Maske, H., Weinges, K.: Untersuchungen über das Verhalten der Meerschweinchen gegenüber verschiedenen diabetogenen Noxen. Alloxan und Dithizon. Arch. exp. Path. Pharmak.230, 406–420 (1957).
Matthews, E.K., Dean, P.M.: Electrical activity in islet cells. In: The Structure and metabolism of pancreatic islets. Ed. Falkmer, S., Hellman, B., Täljedal, I.B. Oxford and New York: Pergamon Press 1970.
Rerup, C., Tarding, F. Streptozotocin and alloxan diabetes in mice. Europ. J. Pharmacol.7, 89–96 (1969).
Schein, P.S., Bates, R.W.: Plasma glucose levels in normal and adrenalectomized mice treated with streptozotocin and nicotinamide. Diabetes18, 760–765 (1968).
—, Cooney, D.A., Vernon, M.L. The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of autitumour activity. Cancer Res.27, 2324–2332 (1967).
—, Loftus, S.: Streptozotocin: depression of mouse liver pyridine nucleotides. Cancer Res.28, 1501–1506 (1968).
Schneyius, A., Täljedal, I.B.: On the mechanism of glucose protection against alloxan toxicity. Diabetologia7, 252–255 (1971).
Villar-Palasi, C., Carbadillo, A., Sols, A., Arteta, J.L.: Sensitivity of pancreas hexokinase towards alloxan and its modification by glucose. Nature180, 387–388 (1957).
Watkins, D., Cooperstein, S.J., Lazarow, A. Effect of alloxan on permeability of pancreatic islet tissue in vitro. Amer. J. Physiol.207, 436–440 (1964).
Webb, J.L.: Alloxan. In: Enzyme and metabolic inhibitors. Vol.3, p. 390. New York: Academic Press 1966.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Dean, P.M., Matthews, E.K. The bioelectrical properties of pancreatic islet cells: Effect of diabetogenic agents. Diabetologia 8, 173–178 (1972). https://doi.org/10.1007/BF01212257
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01212257