Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis

Per Olof Berggren, Shao Nian Yang, Manabu Murakami, Alexander M. Efanov, Sabine Uhles, Martin Köhler, Tilo Moede, Andreas Fernström, Ioulia B. Appelskog, Craig A. Aspinwall, Sergei V. Zaitsev, Olof Larsson, Lina Moitoso De Vargas, Claudia Fecher-Trost, Petra Weißgerber, Andreas Ludwig, Barbara Leibiger, Lisa Juntti-Berggren, Christopher J. Barker, Jesper GromadaMarc Freichel, Ingo B. Leibiger, Veit Flockerzi

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

An oscillatory increase in pancreatic β cell cytoplasmic free Ca 2+ concentration, [Ca2+]i, is a key feature in glucose-induced insulin release. The role of the voltage-gated Ca2+ channel β3 subunit in the molecular regulation of these [Ca 2+]i oscillations has now been clarified by using β3 subunit-deficient β cells. β3 knockout mice showed a more efficient glucose homeostasis compared to wild-type mice due to increased glucose-stimulated insulin secretion. This resulted from an increased glucose-induced [Ca2+]i oscillation frequency in β cells lacking the β3 subunit, an effect accounted for by enhanced formation of inositol 1,4,5-trisphosphate (InsP3) and increased Ca2+ mobilization from intracellular stores. Hence, the β3 subunit negatively modulated InsP3-induced Ca 2+ release, which is not paralleled by any effect on the voltage-gated L type Ca2+ channel. Since the increase in insulin release was manifested only at high glucose concentrations, blocking the β3 subunit in the β cell may constitute the basis for a novel diabetes therapy.

Original languageEnglish (US)
Pages (from-to)273-284
Number of pages12
JournalCell
Volume119
Issue number2
DOIs
StatePublished - Oct 15 2004

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Berggren, P. O., Yang, S. N., Murakami, M., Efanov, A. M., Uhles, S., Köhler, M., Moede, T., Fernström, A., Appelskog, I. B., Aspinwall, C. A., Zaitsev, S. V., Larsson, O., De Vargas, L. M., Fecher-Trost, C., Weißgerber, P., Ludwig, A., Leibiger, B., Juntti-Berggren, L., Barker, C. J., ... Flockerzi, V. (2004). Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. Cell, 119(2), 273-284. https://doi.org/10.1016/j.cell.2004.09.033