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Ca2+-induced Ca2+ release by activation of inositol 1,4,5-trisphosphate receptors in primary pancreatic β-cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2004 (English)In: Cell Calcium, ISSN 0143-4160, E-ISSN 1532-1991, Vol. 36, no 1, p. 1-9Article in journal (Refereed) Published
Abstract [en]

The effect of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) inhibition on the cytoplasmic Ca2+ concentration ([Ca2+]i) was studied in primary insulin-releasing pancreatic β-cells isolated from mice, rats and human subjects as well as in clonal rat insulinoma INS-1 cells. In Ca2+-deficient medium the individual primary β-cells reacted to the SERCA inhibitor cyclopiazonic acid (CPA) with a slow rise of [Ca2+]i followed by an explosive transient elevation. The [Ca2+]i transients were preferentially observed at low intracellular concentrations of the Ca2+ indicator fura-2 and were unaffected by pre-treatment with 100 μM ryanodine. Whereas 20 mM caffeine had no effect on basal [Ca2+]i or the slow rise in response to CPA, it completely prevented the CPA-induced [Ca2+]i transients as well as inositol 1,4,5-trisphosphate-mediated [Ca2+]i transients in response to carbachol. In striking contrast to the primary β-cells, caffeine readily mobilized intracellular Ca2+ in INS-1 cells under identical conditions, and such mobilization was prevented by ryanodine pre-treatment. The results indicate that leakage of Ca2+ from the endoplasmic reticulum after SERCA inhibition is feedback-accelerated by Ca2+-induced Ca2+ release (CICR). In primary pancreatic β-cells this CICR is due to activation of inositol 1,4,5-trisphosphate receptors. CICR by ryanodine receptor activation may be restricted to clonal β-cells.

Place, publisher, year, edition, pages
2004. Vol. 36, no 1, p. 1-9
Keywords [en]
Ca2+-induced Ca2+ release, IP3 receptors, Ryanodine receptors, Insulin secretion, Endoplasmic reticulum, Calcium, Signaling
National Category
Cell and Molecular Biology Physiology Endocrinology and Diabetes
Research subject
Medical Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-72702DOI: 10.1016/j.ceca.2003.11.004 OAI: oai:DiVA.org:uu-72702DiVA, id: diva2:100613
Available from: 2009-02-02 Created: 2008-11-21 Last updated: 2018-01-14Bibliographically approved

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Dyachok, OlegTufveson, GunnarGylfe, Erik

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