Contribution of the endoplasmic reticulum to the glucose-induced [Ca2+]c response in mouse pancreatic islets

Abdelilah Arredouani, Jean Claude Henquin, Patrick Gilon

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Abstract

Thapsigargin (TG), a blocker of Ca2+ uptake by the endoplasmic reticulum (ER), was used to evaluate the contribution of the organelle to the oscillations of cytosolic Ca2+ concentration ([Ca2+]c) induced by repetitive Ca2+ influx ir mouse pancreatic β-cells. Because TG depolarized the plasma membrane in the presence of glucose alone, extracellular K+ was alternated between 10 and 30 mM in the presence of diazoxide to impose membrane potential (MP) oscillations. In control islets, pulses of K+, mimicking regular MP oscillations elicited by 10 mM glucose, induced [Ca2+], oscillations whose nadir remained higher than basal [Ca2+]c. Increasing the depolarization phase of the pulses while keeping their frequency constant (to mimic the effects of a further rise of the glucose concentration on MP) caused an upward shift of the nadir of [Ca2+]c oscillations that was reproduced by raising extracellular Ca2+ (to increase Ca2+ influx) with. out changing the pulse protocol. In TG-pretreated islets, the imposed [Ca2+]c oscillations were of much larger amplitude than in control islets and occurred on basal levels. During intermittent trains of depolarizations, control islets displayed mixed [Ca2+]c oscillations characterized by a summa. tion of fast oscillations on top of slow ones, whereas nc progressive summation of the fast oscillations was observed in TG-pretreated islets. In conclusion, the buffering capacity of the ER in pancreatic β-cells limits the amplitude of [Ca2+]c oscillations and may explain how the nadir between oscillations remains above baseline during regular oscillations or gradually increases during mixed [Ca2+]c oscillations, two types of response observed during glucose stimulation.

Original languageEnglish
Pages (from-to)E982-E991
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume282
Issue number5 45-5
Publication statusPublished - 29 Jun 2002

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Keywords

  • Cytosolic Ca concentration oscillations
  • Endoplasmic reticulum
  • Pancreatic β-cell
  • Thapsigargin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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