Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice

Schulla, Verena; Renström, Erik; Feil, Robert; Feil, Susanne; Franklin, Isobel; Gjinovci, Aslan; Jing, Xing-Jun; Laux, Dirk; Lundquist, Ingmar; Magnuson, Mark A; Obermüller, Stefanie; Olofsson, Charlotta S; Salehi, Albert; Wendt, Anna; Klugbauer, Norbert; Wollheim, Claes; Rorsman, Patrik; Hofmann, Franz

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Title		Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice
Authors		Schulla, Verena Renström, Erik Feil, Robert Feil, Susanne Franklin, Isobel Gjinovci, Aslan Jing, Xing-Jun Laux, Dirk Lundquist, Ingmar Magnuson, Mark A Obermüller, Stefanie Olofsson, Charlotta S Salehi, Albert Wendt, Anna Klugbauer, Norbert Wollheim, Claes Rorsman, Patrik Hofmann, Franz show all authors [1 - 18]
Published in		EMBO Journal. 2003, vol. 22, no. 15, p. 3844-54
Abstract		Insulin is secreted from pancreatic beta cells in response to an elevation of cytoplasmic Ca(2+) resulting from enhanced Ca(2+) influx through voltage-gated Ca(2+) channels. Mouse beta cells express several types of Ca(2+) channel (L-, R- and possibly P/Q-type). beta cell-selective ablation of the gene encoding the L-type Ca(2+) channel subtype Ca(v)1.2 (betaCa(v)1.2(-/-) mouse) decreased the whole-cell Ca(2+) current by only approximately 45%, but almost abolished first-phase insulin secretion and resulted in systemic glucose intolerance. These effects did not correlate with any major effects on intracellular Ca(2+) handling and glucose-induced electrical activity. However, high-resolution capacitance measurements of exocytosis in single beta cells revealed that the loss of first-phase insulin secretion in the betaCa(v)1.2(-/-) mouse was associated with the disappearance of a rapid component of exocytosis reflecting fusion of secretory granules physically attached to the Ca(v)1.2 channel. Thus, the conduit of Ca(2+) entry determines the ability of the cation to elicit secretion.
Keywords		Animals — Base Sequence — Calcium Channels, L-Type/genetics/physiology — DNA Primers — Exocytosis — Insulin/secretion — Insulin Resistance — Islets of Langerhans/physiology/secretion — Mice
Identifiers		DOI: 10.1093/emboj/cdg389 PMID: 12881419
Full text		Article (Published version) (371 Kb) - Free access
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
Citation (ISO format)		SCHULLA, Verena et al. Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice. In: EMBO Journal, 2003, vol. 22, n° 15, p. 3844-54. https://archive-ouverte.unige.ch/unige:34552