Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network

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Bibtex

@article{01d3fb3ae8f9468aac46d177be2f26e6,
title = "Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network",
abstract = "The neural cell adhesion molecule (NCAM) is required for cell type segregation during pancreatic islet organogenesis. We have investigated the functional consequences of ablating NCAM on pancreatic beta-cell function. In vivo, NCAM(-/-) mice exhibit impaired glucose tolerance and basal hyperinsulinemia. Insulin secretion from isolated NCAM(-/-) islets is enhanced at glucose concentrations below 15 mM but inhibited at higher concentrations. Glucagon secretion from pancreatic alpha-cells evoked by low glucose was also severely impaired in NCAM(-/-) islets. The diminution of insulin secretion is not attributable to defective glucose metabolism or glucose sensing (documented as glucose-induced changes in intracellular Ca2+ and K-ATP-channel activity). Resting K-ATP conductance was lower in NCAM(-/-) beta-cells than wild-type cells, and this difference was abolished when F-actin was disrupted by cytochalasin D (1 mu M). In wild-type beta-cells, the submembrane actin network disassembles within 10 min during glucose stimulation (30 mM), an effect not seen in NCAM(-/-) beta-cells. Cytochalasin D eliminated this difference and normalized insulin and glucagon secretion in NCAM(-/-) islets. Capacitance measurements of exocytosis indicate that replenishment of the readily releasable granule pool is suppressed in NCAM(-/-) alpha- and beta-cells. Our data suggest that remodeling of the submembrane actin network is critical to normal glucose regulation of both insulin and glucagon secretion. (Endocrinology 150: 3067-3075, 2009)",
author = "Olofsson, {Charlotta S.} and Joakim Hakansson and Albert Salehi and Martin Bengtsson and Juris Galvanovskis and Chris Partridge and {S{\"o}rhede Winzell}, Maria and Xiaojie Xian and Lena Eliasson and Ingmar Lundquist and Henrik Semb and Patrik Rorsman",
year = "2009",
doi = "10.1210/en.2008-0475",
language = "English",
volume = "150",
pages = "3067--3075",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "Endocrine Society",
number = "7",

}