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• W2079230681 endingPage "27913" @default.
• W2079230681 startingPage "27905" @default.
• W2079230681 abstract "The effects of a transient exposure to hydrogen peroxide (10 min at 200 μmH₂O₂) on pancreatic beta cell signal transduction and insulin secretion have been evaluated. In rat islets, insulin secretion evoked by glucose (16.7 mm) or by the mitochondrial substrate methyl succinate (5 mm) was markedly blunted following exposure to H₂O₂. In contrast, the secretory response induced by plasma membrane depolarization (20 mm KCl) was not significantly affected. Similar results were obtained in insulinoma INS-1 cells using glucose (12.8 mm) as secretagogue. After H₂O₂ treatment, glucose no longer depolarized the membrane potential (ΔΨ) of INS-1 cells or increased cytosolic Ca²⁺. Both ΔΨ and Ca²⁺ responses were still observed with 30 mm KCl despite an elevated baseline of cytosolic Ca²⁺ appearing ∼10 min after exposure to H₂O₂. The mitochondrial ΔΨ of INS-1 cells was depolarized by H₂O₂ abolishing the hyperpolarizing action of glucose. These ΔΨ changes correlated with altered mitochondrial morphology; the latter was not preserved by the overexpression of the antiapoptotic protein Bcl-2. Mitochondrial Ca²⁺ was increased following exposure to H₂O₂ up to the micromolar range. No further augmentation occurred after glucose addition, which normally raises this parameter. Nevertheless, KCl was still efficient in enhancing mitochondrial Ca²⁺. Cytosolic ATP was markedly reduced by H₂O₂ treatment, probably explaining the decreased endoplasmic reticulum Ca²⁺. Taken together, these data point to the mitochondria as primary targets for H₂O₂ damage, which will eventually interrupt the transduction of signals normally coupling glucose metabolism to insulin secretion." @default.
• W2079230681 created "2016-06-24" @default.
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• W2079230681 date "1999-09-01" @default.
• W2079230681 modified "2023-10-18" @default.
• W2079230681 title "Hydrogen Peroxide Alters Mitochondrial Activation and Insulin Secretion in Pancreatic Beta Cells" @default.
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• W2079230681 doi "https://doi.org/10.1074/jbc.274.39.27905" @default.
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