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

Salvatore Antonucci1,2, Alessia Tagliavini3, Morten Gram Pedersen3

  • 1a Department of Biomedical Sciences ; University of Padua ; Padua , Italy.

Islets
|January 7, 2016
PubMed

Insights

Reactive oxygen/nitrogen species (ROS/RNS) disrupt calcium (Ca2+) oscillations in pancreatic beta cells, impacting insulin secretion. This study reveals ROS/RNS interfere with endoplasmic reticulum Ca2+ handling, linking them to diabetes pathogenesis.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Biochemistry

Background:

  • Pulsatile insulin secretion and Ca2+ oscillations in pancreatic beta cells are crucial for glucose homeostasis.
  • Disturbances in these processes are early indicators of diabetes.
  • The role of reactive oxygen/nitrogen species (ROS/N) in beta cell dysfunction is increasingly recognized, with evidence suggesting they target key Ca2+ regulatory proteins.

Purpose of the Study:

  • To investigate the hypothesis that ROS/RNS disrupt Ca2+ oscillations and subsequent insulin pulsatility.
  • To elucidate the mechanisms by which ROS/RNS affect Ca2+ handling in pancreatic beta cells.

Main Methods:

  • Utilized photoactivation of aluminum phthalocyanine chloride (AlClPc) to generate ROS/RNS in MIN6 beta cells.
  • Applied the sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor thapsigargin.
  • Employed a mathematical model of Ca2+ handling adapted to MIN6 cells for theoretical analysis.

Main Results:

  • ROS/RNS, depending on concentration, either abolished or accelerated Ca2+ oscillations in MIN6 cells.
  • Thapsigargin modulated the cellular response to high ROS/RNS concentrations.
  • Thapsigargin's effects mimicked those of moderate ROS/RNS exposure, suggesting interference with endoplasmic reticulum Ca2+ handling.

Conclusions:

  • ROS/RNS directly impact Ca2+ oscillation dynamics in pancreatic beta cells.
  • Endoplasmic reticulum Ca2+ handling is a key target for ROS/RNS-induced beta cell dysfunction.
  • These findings establish a potential link between ROS/RNS and the disturbed pulsatile insulin secretion observed in diabetes.
Keywords:
ROS/RNScalcium pumpsmathematical modelingphotosensitizerpulsatile insulin secretion

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