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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
Jing, Xing-Jun
Laux, Dirk
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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 AnimalsBase SequenceCalcium Channels, L-Type/genetics/physiologyDNA PrimersExocytosisInsulin/secretionInsulin ResistanceIslets of Langerhans/physiology/secretionMice
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PMID: 12881419
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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

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Deposited on : 2014-03-03

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