Reactive oxygen and nitrogen species disturb Ca(2+) oscillations in insulin-secreting MIN6 ?-cells.

ABSTRACT: Disturbances in pulsatile insulin secretion and Ca(2+) oscillations in pancreatic ?-cells are early markers of diabetes, but the underlying mechanisms are still incompletely understood. Reactive oxygen/nitrogen species (ROS/RNS) are implicated in reduced ?-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 ?-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.

SUBMITTER: Antonucci S 

PROVIDER: S-EPMC4878267 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature