Hydrogen peroxide generation in whole rat pancreatic islets; synergistic regulation by cytoplasmic free calcium and protein kinase-C.
This is the first report to show that pancreatic islet cells generate H2O2 and this H2O2 generation is regulated synergistically by cytoplasmic free calcium ([Ca2+]i) and protein kinase-C. Effects of calcium ionophore A23187 and 12-O-tetradecanoylphorbol 13-acetate (TPA), a tumor promoter, on H2O2 generation were studied in whole pancreatic islets obtained from male Wistar rats. We employed A23187 to elevate cytoplasmic free calcium, and TPA to activate protein kinase-C and monitored continuously their effects on H2O2 generation, measured using homovanillic acid and horseradish peroxidase. A23187 stimulates H2O2 generation. TPA, which activates protein kinase-C, augments this A23187-stimulated H2O2 generation. H2O2 generation is stimulated by an increase in [Ca2+]i and regulated synergistically by [Ca2+]i and protein kinase-C.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004357:Drug Synergism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000001:Calcimycin; D006861:Hydrogen Peroxide; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium