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 Gromada & 3 others Marc Freichel, Ingo B. Leibiger, Veit Flockerzi

Research output: Contribution to journalArticle

88 Citations (Scopus)

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

Fingerprint

Exocytosis
Insulin
Glucose
Inositol 1,4,5-Trisphosphate
Electric potential
Medical problems
Knockout Mice
Homeostasis

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Berggren, P. O., Yang, S. N., Murakami, M., Efanov, A. M., Uhles, S., Köhler, M., ... 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

Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. / Berggren, Per Olof; Yang, Shao Nian; Murakami, Manabu; Efanov, Alexander M.; Uhles, Sabine; Köhler, Martin; Moede, Tilo; Fernström, Andreas; Appelskog, Ioulia B.; Aspinwall, Craig A.; Zaitsev, Sergei V.; Larsson, Olof; De Vargas, Lina Moitoso; Fecher-Trost, Claudia; Weißgerber, Petra; Ludwig, Andreas; Leibiger, Barbara; Juntti-Berggren, Lisa; Barker, Christopher J.; Gromada, Jesper; Freichel, Marc; Leibiger, Ingo B.; Flockerzi, Veit.

In: Cell, Vol. 119, No. 2, 15.10.2004, p. 273-284.

Research output: Contribution to journalArticle

Berggren, PO, Yang, SN, Murakami, M, Efanov, AM, Uhles, S, Köhler, M, Moede, T, Fernström, A, Appelskog, IB, Aspinwall, CA, Zaitsev, SV, Larsson, O, De Vargas, LM, Fecher-Trost, C, Weißgerber, P, Ludwig, A, Leibiger, B, Juntti-Berggren, L, Barker, CJ, Gromada, J, Freichel, M, Leibiger, IB & Flockerzi, V 2004, 'Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis', Cell, vol. 119, no. 2, pp. 273-284. https://doi.org/10.1016/j.cell.2004.09.033
Berggren PO, Yang SN, Murakami M, Efanov AM, Uhles S, Köhler M et al. Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. Cell. 2004 Oct 15;119(2):273-284. https://doi.org/10.1016/j.cell.2004.09.033
Berggren, Per Olof ; Yang, Shao Nian ; Murakami, Manabu ; Efanov, Alexander M. ; Uhles, Sabine ; Köhler, Martin ; Moede, Tilo ; Fernström, Andreas ; Appelskog, Ioulia B. ; Aspinwall, Craig A. ; Zaitsev, Sergei V. ; Larsson, Olof ; De Vargas, Lina Moitoso ; Fecher-Trost, Claudia ; Weißgerber, Petra ; Ludwig, Andreas ; Leibiger, Barbara ; Juntti-Berggren, Lisa ; Barker, Christopher J. ; Gromada, Jesper ; Freichel, Marc ; Leibiger, Ingo B. ; Flockerzi, Veit. / Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis. In: Cell. 2004 ; Vol. 119, No. 2. pp. 273-284.
@article{e803ba34389442db964b8b0ec2cfa20a,
title = "Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis",
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.",
author = "Berggren, {Per Olof} and Yang, {Shao Nian} and Manabu Murakami and Efanov, {Alexander M.} and Sabine Uhles and Martin K{\"o}hler and Tilo Moede and Andreas Fernstr{\"o}m and Appelskog, {Ioulia B.} and Aspinwall, {Craig A.} and Zaitsev, {Sergei V.} and Olof Larsson and {De Vargas}, {Lina Moitoso} and Claudia Fecher-Trost and Petra Wei{\ss}gerber and Andreas Ludwig and Barbara Leibiger and Lisa Juntti-Berggren and Barker, {Christopher J.} and Jesper Gromada and Marc Freichel and Leibiger, {Ingo B.} and Veit Flockerzi",
year = "2004",
month = "10",
day = "15",
doi = "10.1016/j.cell.2004.09.033",
language = "English",
volume = "119",
pages = "273--284",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - Removal of Ca2+ channel β3 subunit enhances Ca2+ oscillation frequency and insulin exocytosis

AU - Berggren, Per Olof

AU - Yang, Shao Nian

AU - Murakami, Manabu

AU - Efanov, Alexander M.

AU - Uhles, Sabine

AU - Köhler, Martin

AU - Moede, Tilo

AU - Fernström, Andreas

AU - Appelskog, Ioulia B.

AU - Aspinwall, Craig A.

AU - Zaitsev, Sergei V.

AU - Larsson, Olof

AU - De Vargas, Lina Moitoso

AU - Fecher-Trost, Claudia

AU - Weißgerber, Petra

AU - Ludwig, Andreas

AU - Leibiger, Barbara

AU - Juntti-Berggren, Lisa

AU - Barker, Christopher J.

AU - Gromada, Jesper

AU - Freichel, Marc

AU - Leibiger, Ingo B.

AU - Flockerzi, Veit

PY - 2004/10/15

Y1 - 2004/10/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=5444225799&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5444225799&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2004.09.033

DO - 10.1016/j.cell.2004.09.033

M3 - Article

VL - 119

SP - 273

EP - 284

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -