Oxidative stress causes depolarization and calcium uptake in the rat insulinoma cell RINm5F.
Generation of free radicals and oxidative stress play a role in the development of islet dysfunction in diabetes. These mechanisms are known to affect membrane potential and cytosolic calcium in other cell types. The effect of oxidative stress, caused by tert-butyl-hydroperoxide (BuOOH), was therefore studied with respect to the redox ratio of glutathione, membrane potential, cytosolic calcium and insulin release in the insulin-secreting RINm5F cell. In RINm5F cells BuOOH decreased the redox ratio of glutathione and caused depolarization. This was associated with an increase in cytosolic calcium and insulin secretion. The effects of BuOOH on cytosolic calcium and insulin release were abolished in the absence of extracellular calcium and decreased by the calcium channel blocker verapamil. Our data suggest that in RINm5F cells oxidative stress causes insulin release by depolarization and subsequent calcium entry through voltage-dependent calcium channels.
Department of Pharmacology, Institute of Pharmaceutical Sciences, Eberhard-Karls-University, Tübingen, Germany.
M A
MA
Wahl
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I
Koopmann
H P
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Ammon
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma / Q000473:pathology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
D007328:Insulin; D011189:Potassium Chloride; D020122:tert-Butylhydroperoxide; D005978:Glutathione; D002118:Calcium