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

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Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network. / Olofsson, Charlotta S.; Hakansson, Joakim; Salehi, Albert; Bengtsson, Martin; Galvanovskis, Juris; Partridge, Chris; Sörhede Winzell, Maria; Xian, Xiaojie; Eliasson, Lena; Lundquist, Ingmar; Semb, Henrik; Rorsman, Patrik.

In: Endocrinology, Vol. 150, No. 7, 2009, p. 3067-3075.

Research output: Contribution to journalArticle

Harvard

Olofsson, CS, Hakansson, J, Salehi, A, Bengtsson, M, Galvanovskis, J, Partridge, C, Sörhede Winzell, M, Xian, X, Eliasson, L, Lundquist, I, Semb, H & Rorsman, P 2009, 'Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network', Endocrinology, vol. 150, no. 7, pp. 3067-3075. https://doi.org/10.1210/en.2008-0475

APA

Olofsson, C. S., Hakansson, J., Salehi, A., Bengtsson, M., Galvanovskis, J., Partridge, C., ... Rorsman, P. (2009). Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network. Endocrinology, 150(7), 3067-3075. https://doi.org/10.1210/en.2008-0475

CBE

Olofsson CS, Hakansson J, Salehi A, Bengtsson M, Galvanovskis J, Partridge C, Sörhede Winzell M, Xian X, Eliasson L, Lundquist I, Semb H, Rorsman P. 2009. Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network. Endocrinology. 150(7):3067-3075. https://doi.org/10.1210/en.2008-0475

MLA

Vancouver

Author

Olofsson, Charlotta S. ; Hakansson, Joakim ; Salehi, Albert ; Bengtsson, Martin ; Galvanovskis, Juris ; Partridge, Chris ; Sörhede Winzell, Maria ; Xian, Xiaojie ; Eliasson, Lena ; Lundquist, Ingmar ; Semb, Henrik ; Rorsman, Patrik. / Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network. In: Endocrinology. 2009 ; Vol. 150, No. 7. pp. 3067-3075.

RIS

TY - JOUR

T1 - Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule(-/-) Mice Due to Defective Reorganization of the Submembrane F-Actin Network

AU - Olofsson, Charlotta S.

AU - Hakansson, Joakim

AU - Salehi, Albert

AU - Bengtsson, Martin

AU - Galvanovskis, Juris

AU - Partridge, Chris

AU - Sörhede Winzell, Maria

AU - Xian, Xiaojie

AU - Eliasson, Lena

AU - Lundquist, Ingmar

AU - Semb, Henrik

AU - Rorsman, Patrik

PY - 2009

Y1 - 2009

N2 - 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)

AB - 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)

U2 - 10.1210/en.2008-0475

DO - 10.1210/en.2008-0475

M3 - Article

VL - 150

SP - 3067

EP - 3075

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 7

ER -