The bioelectrical properties of pancreatic islet cells: Effect of diabetogenic agents

Abstract

Alloxan 5 mM depolarised the islet but not the aeinar cells of mouse pancreatic segments in vitro. This effect was prevented by D-glucose but not by glutathione, 3, 0, methyl-e-D-glucose, D-glucosamine, D-mannoheptulose, or L-leucine. Pretreatment of islet /?-cells with streptozotocin 20 mM caused no depolarization but inhibited the generation of action potentials by D-glucose, L-leueine, 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 streptozotoein action. These observations are discussed in relation to the diabetogenic action of alloxan and streptozotocin. Propridt~s biodlectriques des cellules des ~lots pancrdatiques: Effets des agents diabdtog~nes Rgsumd. L'alloxane (5 raM) a d6polarisd les cellules des ilots, mais non les cellules de l'acinus des segments pancrdatiques chez la souris in vitro. Cet effet 6tait ani-hil6 par le D-glucose, mais non par le glutathion, le 3, 0, mdthyl-~-D-glueose, la D-glucosamine, le D-mannoheptulose ou la L-leucine. Le pr6-traitement des eellules fl des ilots ~ la streptozotoeine (20 mM) n'a pas provoqu6 de d6polarisation, mais a inhibd la gdngration de potentiels d'action par le D-glucose, la L'leueine, le D-mannose et la D-glyc6ralddhyde, tandis que les potentiels d'action pro-voqu~s par la tolbutamide n'dtaient pus bloquds; la partie alkylante de la strep~ozotoeine, la N-nitroso-Nmgthyl ur6e produisaient les mgmes effets. L'exposition prdalable des cellules des ilots ~ l'amide nicotinique (4.1 mM) fournissait une protection contre l'aetion de la streptozotoeine. Ces observations sont diseut~es en relation avee Faction diabdtoggne de l'Mloxane et de la streptozotocine. Die bioelektrischen Eigenschaften yon Inselzellen des Pankreas: Wirkungen diabetogener Substanzen Zusammenfassung. 5 mM Alloxan depolaiisiert die Inseln abet nicht die Azinuszelleu yon Segmenten des M/~usepankre~s in vitro. Diese Wirkung konnte dutch D-Glucose abet nicht durch Glutathion, 3, 0, methyl-e-D-Glucose, D-Glucosamin, D-Mannoheptulose, oder L-Leuein verhindert werden. Die Vorbehandlung yon fl-Zellen der Inseln mit 20ram Streptozotocin verursachte keine Depolarisierung abet verhinderte die Erzeugung von AktionspotentiMen durch D-Glucose, L-Leuein, D-Mannose und D-Glyceraldehyden, w/ihrend durch Tolbutamid induzierte AktionspotentiMe nieht bloekiert wurden. Der alkylierende Tell yon Streptozotocin, der N-nitroso-N-methyl-Harnstoff zeigte /ihnliche Wirkunten. Ein vorheriger Kontakt der Inselzellen mit Nieotinamid 4,1 mM erzeugte einen Schutz gegeniiber der Streptozotocinwirkung. Diese Beobachtungen werden in Verbindung mit der diabetogenen Wirkung von Alloxan und Streptozotocin diskutiert.

Barbiturates inhibit ATP‐K+ channels and voltage‐activated currents in CRI‐G1 insulin‐secreting cells

“…2 Author for correspondence. (Dean & Matthews, 1972). Some of the results presented here have already appeared in abstract form (Ashford et al, 1989;Kozlowski et al, 1989a).…”

Alloxan-induced alteration of insulin release, rubidium efflux and glucose metabolism in rat islets stimulated by various secretagogues

“…In mouse islets alloxan produces depolarization of Bcells [5] and inhibition of the univalent cation pump [6]. In rat islets it produces a loss of membraneassociated particles [7].…”

“…Although this increase in K-permeability could conceivably be the result of damage to the cell membrane, several arguments do not support this possibility: (a) the effect is transient even when alloxan is present for 15 min; (b) it is not accompanied by a leak of insulin in our system; (c) a similar dose of aUoxan does not augment the permeability of rat islet cell membranes to sucrose [9]; and (d) it is quickly reversed by glyceraldehyde, tolbutamide and aketoisocaproic acid. We would suggest rather that the blockade [6] of an electrogenic Na/K pump [27] is, at least partially, the cause of the depolarization measured in alloxan treated B-cells [5] and that the increase in 86Rb efflux is the consequence of this fall in membrane potential. The possible interrelationships between ionic, electrical and metabolic changes produced by alloxan are difficult to evaluate.…”

Pancreatic islet cells: effects of monosaccharides, glycolytic intermediates and metabolic inhibitors on membrane potential and electrical activity.

“…On the other hand, phosphorylation of even restricted amounts of Dglyceraldehyde will lead to ATP production and a flux of intermediates through the lower span of the glycolytic pathway. Our previous work (Dean & Matthews, 1972) has shown that to remain an effective stimulant D-glyceraldehyde requires an intact NAD+/NADH redox system, for the electrical activity elicited by glyceraldehyde (and by glucose) is obliterated by streptozotocin, a diabetogenic agent which severely reduces NAD levels in islet cells (Schein, Cooney, McMenamin & Anderson, 1973). Furthermore, glucose metabolism in islet cells is normally associated with a very rapid and marked increase in reduced pyridine nucleotides (Panten, Dal Ri, Poser & Hasselblatt, 1971) which is not seen in the absence of Ca2+.…”