A short exposure to a high‐glucose milieu stabilizes the acidic vacuolar apparatus of insulinoma cells in culture to ensuing oxidative stress

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Abstract
It was recently suggested that extracellular hydrogen peroxide, after diffusing into and throughout adjacent cells ‐ which may be the case if they have only a weak capacity to degrade hydrogen peroxide ‐ labilizes their lysosomal compartment due to its content of low‐molecular‐weight iron in redox‐active form. The iron would be present as a consequence of normal autophagocytotic degradation of various iron‐containing metalloproteins. Beta‐ and insulinoma cells are especially vulnerable to oxidative stress, since they possess only low capacity to degrade hydrogen peroxide, and, perhaps, since they normally have a certain degree of autophagocytotic degradation of secretory granules with some iron content ‐ crinophagy. The toxicity to beta cells of oxidative stress, such as an exposure to alloxan, that results in extracellular formation of hydrogen peroxide, is considerably reduced if animals are initially given an intravenous bolus dose of glucose, temporarily bringing up the blood level to about 20 mM. In this study it was demonstrated that already as short an exposure as 30 min to 20 mM D‐glucose reduces the sensitivity of HIT and NIT insulinoma cells in culture to a subsequent exposure to hydrogen peroxide. In parallel, exposure to such a high‐glucose medium also reduces their desferrioxamine‐available amount of iron and, moreover, stabilizes their lysosomal membranes against oxidative stress ‐ thus preventing diffusion to the cytosol of damaging lysosomal contents following iron‐catalyzed, Fenton‐type, intralysosomal reactions. We suggest that both general autophagocytotic turnover and, in particular, crinophagy of secretory granules are decreased by an increased glucose concentration of the surrounding milieu, with attendant reduced amounts of intralysosomal low‐molecular‐weight iron and, thus, diminished sensitivity to oxidative stress.