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Impaired insulin secretion and glucose tolerance in β cell‐selective Ca V 1.2 Ca 2+ channel null mice
Author(s) -
Schulla Verena,
Renström Erik,
Feil Robert,
Feil Susanne,
Franklin Isobel,
Gjinovci Asllan,
Jing XingJun,
Laux Dirk,
Lundquist Ingmar,
Magnuson Mark A.,
Obermüller Stefanie,
Olofsson Charlotta S.,
Salehi Albert,
Wendt Anna,
Klugbauer Norbert,
Wollheim Claes B.,
Rorsman Patrik,
Hofmann Franz
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg389
Subject(s) - exocytosis , biology , medicine , endocrinology , secretion , insulin , beta cell , intracellular , extracellular , beta (programming language) , microbiology and biotechnology , islet , computer science , programming language
Insulin is secreted from pancreatic β cells in response to an elevation of cytoplasmic Ca 2+ resulting from enhanced Ca 2+ influx through voltage‐gated Ca 2+ channels. Mouse β cells express several types of Ca 2+ channel (L‐, R‐ and possibly P/Q‐type). β cell‐selective ablation of the gene encoding the L‐type Ca 2+ channel subtype Ca v 1.2 (βCa v 1.2 −/− mouse) decreased the whole‐cell Ca 2+ current by only ∼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 β cells revealed that the loss of first‐phase insulin secretion in the βCa 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.