Disturbances in pulsatile insulin secretion and Ca2+ 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 Ca2+ pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca2+ oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca2+ oscillations in the MIN6 -cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor thapsigargin modifies the Ca2+ 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 Ca2+ handling. This idea is supported by theoretical studies using a mathematical model of Ca2+ handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion.

Reactive oxygen and nitrogen species disturb Ca2+ oscillations in insulin-secreting MIN6 β-cells

ANTONUCCI, SALVATORE;TAGLIAVINI, ALESSIA;PEDERSEN, MORTEN GRAM
2015

Abstract

Disturbances in pulsatile insulin secretion and Ca2+ 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 Ca2+ pumps and channels. Thus, we hypothesized that ROS/RNS could disturb Ca2+ oscillations and downstream insulin pulsatility. We show that ROS/RNS production by photoactivation of aluminum phthalocyanine chloride (AlClPc) abolish or accelerate Ca2+ oscillations in the MIN6 -cell line, depending on the amount of ROS/RNS. Application of the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor thapsigargin modifies the Ca2+ 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 Ca2+ handling. This idea is supported by theoretical studies using a mathematical model of Ca2+ handling adapted to MIN6 cells. Our results suggest a putative link between ROS/RNS and disturbed pulsatile insulin secretion.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3190195
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