title: Impaired insulin secretion and glucose tolerance in beta cell-selective Ca(v)1.2 Ca2+ channel null mice.
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.
authors.affiliation: Institut für Pharmakologie und Toxikologie, TU München, Biedersteiner Strasse 29, D-80802 München, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Schulla
authors.forename: Erik
authors.initials: E
authors.lastname: Renström
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.forename: Susanne
authors.initials: S
authors.lastname: Feil
authors.forename: Isobel
authors.initials: I
authors.lastname: Franklin
authors.forename: Asllan
authors.initials: A
authors.lastname: Gjinovci
authors.forename: Xing-Jun
authors.initials: XJ
authors.lastname: Jing
authors.forename: Dirk
authors.initials: D
authors.lastname: Laux
authors.forename: Ingmar
authors.initials: I
authors.lastname: Lundquist
authors.forename: Mark A
authors.initials: MA
authors.lastname: Magnuson
authors.forename: Stefanie
authors.initials: S
authors.lastname: Obermüller
authors.forename: Charlotta S
authors.initials: CS
authors.lastname: Olofsson
authors.forename: Albert
authors.initials: A
authors.lastname: Salehi
authors.forename: Anna
authors.initials: A
authors.lastname: Wendt
authors.forename: Norbert
authors.initials: N
authors.lastname: Klugbauer
authors.forename: Claes B
authors.initials: CB
authors.lastname: Wollheim
authors.forename: Patrik
authors.initials: P
authors.lastname: Rorsman
authors.forename: Franz
authors.initials: F
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology*; D017931:DNA Primers; D005089:Exocytosis; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D051379:Mice
chemical_list: D020746:Calcium Channels, L-Type; D017931:DNA Primers; D007328:Insulin; C419385:L-type calcium channel alpha(1C)