title: Reactive oxygen and nitrogen species disturb Ca(2+) oscillations in insulin-secreting MIN6 β-cells.
abstract: Disturbances in pulsatile insulin secretion and Ca(2+) oscillations in pancreatic β-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced β-cell function, and ROS/RNS target several Ca(2+) pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca(2+) oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca(2+) oscillations in the MIN6 β-cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) inhibitor thapsigargin modifies the Ca(2+) response to high concentrations of ROS/RNS. Further, thapsigargin produces effects that resemble those elicited by moderate ROS/RNS production. These results indicate that ROS/RNS interfere with endoplasmic reticulum Ca(2+) handling. This idea is supported by theoretical studies using a mathematical model of Ca(2+) handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion.
authors.affiliation: a Department of Biomedical Sciences ; University of Padua ; Padua , Italy.|b Venetian Institute of Molecular Medicine ; Padua , Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Antonucci
authors.affiliation: c Department of Information Engineering ; University of Padua ; Padua , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Tagliavini
authors.affiliation: c Department of Information Engineering ; University of Padua ; Padua , Italy.
authors.forename: Morten Gram
authors.initials: MG
authors.lastname: Pedersen
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D002478:Cells, Cultured; D005947:Glucose / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism
chemical_list: D007211:Indoles; D009942:Organometallic Compounds; D015221:Potassium Channels; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C044797:chloroaluminum phthalocyanine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D005947:Glucose
keywords: ROS/RNS; calcium pumps; mathematical modeling; photosensitizer; pulsatile insulin secretion