SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca2+ pumps for Ca2+ homeostasis in pancreatic βcells

Abdelilah Arredouani, Yves Guiot, Jean Christophe Jonas, Lynne H. Liu, Myriam Nenquin, José A. Pertusa, Jacques Rahier, Jean François Rolland, Gary E. Shull, Martine Stevens, Frank Wuytack, Jean Claude Henquin, Patrick Gilon

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Abstract

Two sarcoendoplasmic reticulum Ca2+-ATPases, SERCA3 and SERCA2b, are expressed in pancreatic islets. Immunocytochemistry showed that SERCA3 is restricted to β-cells in the mouse pancreas. Control and SERCA3-deficient mice were used to evaluate the role of SERCA3 in β-cell cytosolic-free Ca2+ concentration ([Ca2+]c) regulation, insulin secretion, and glucose homeostasis. Basal [Ca2+]c increased by SERCA3 ablation. Stimulation with glucose induced a transient drop in basal [Ca2+]c that was suppressed by inhibition of all SERCAs with thapsigargin (TG) but unaffected by selective SERCA3 ablation. Ca2+ mobilization by acetylcholine was normal in SERCA3-deficient βcells. In contrast, [Ca2+]c oscillations resulting from intermittent glucose-stimulated Ca2+ influx and [Ca2+]c transients induced by pulses of high K+ were similarly affected by SERCA3 ablation or TG pretreatment of control islets; their amplitude was increased and their slow descending phase suppressed. This suggests that, during the decay of each oscillation, the endoplasmic reticulum releases Ca2+ that was pumped by SERCA3 during the upstroke phase. SERCA3 ablation increased the insulin response of islets to 15 mmol/l glucose. However, basal and postprandial plasma glucose and insulin concentrations in SERCA3-deficient mice were normal. In conclusion, SERCA2b, but not SERCA3, is involved in basal [Ca2+]c regulation in β-cells. SERCA3 becomes operative when [Ca2+]c rises and is required for normal [Ca2+]c oscillations in response to glucose. However, a lack of SERCA3 is insufficient in itself to alter glucose homeostasis or impair insulin secretion in mice.

Original languageEnglish
Pages (from-to)3245-3253
Number of pages9
JournalDiabetes
Volume51
Issue number11
DOIs
Publication statusPublished - 1 Nov 2002

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Arredouani, A., Guiot, Y., Jonas, J. C., Liu, L. H., Nenquin, M., Pertusa, J. A., Rahier, J., Rolland, J. F., Shull, G. E., Stevens, M., Wuytack, F., Henquin, J. C., & Gilon, P. (2002). SERCA3 ablation does not impair insulin secretion but suggests distinct roles of different sarcoendoplasmic reticulum Ca2+ pumps for Ca2+ homeostasis in pancreatic βcells. Diabetes, 51(11), 3245-3253. https://doi.org/10.2337/diabetes.51.11.3245