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Impaired insulin ex...
Impaired insulin exocytosis in neural cell adhesion molecule-/- mice due to defective reorganization of the submembrane F-actin network.
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- Olofsson, Charlotta S, 1971 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi,Institute of Neuroscience and Physiology, Department of Physiology
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Håkansson, Joakim (author)
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Salehi, Albert (author)
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Bengtsson, Martin (author)
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Galvanovskis, Juris (author)
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Partridge, Chris (author)
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SörhedeWinzell, Maria (author)
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- Xian, Xiaojie (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Eliasson, Lena (author)
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Lundquist, Ingmar (author)
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- Semb, Henrik (author)
- Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine
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Rorsman, Patrik, 1959 (author)
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- Sörhede Winzell, Maria (author)
- Lund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine
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(creator_code:org_t)
- 2009-02-12
- 2009
- English.
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In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:7, s. 3067-75
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Abstract
Subject headings
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- 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 Ca(2+) 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 muM). 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Physiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Actins
- metabolism
- Adenosine Triphosphate
- metabolism
- Animals
- Exocytosis
- physiology
- Female
- Glucagon
- secretion
- Glucose
- physiology
- Glucose Intolerance
- genetics
- Insulin
- physiology
- secretion
- Islets of Langerhans
- physiology
- Mice
- Mice
- Knockout
- Neural Cell Adhesion Molecules
- deficiency
- Patch-Clamp Techniques
- Potassium Channels
- Inwardly Rectifying
- metabolism
Publication and Content Type
- ref (subject category)
- art (subject category)
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Olofsson, Charlo ...
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Håkansson, Joaki ...
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Salehi, Albert
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Bengtsson, Marti ...
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Galvanovskis, Ju ...
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Partridge, Chris
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SörhedeWinzell, ...
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Xian, Xiaojie
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Eliasson, Lena
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Lundquist, Ingma ...
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Semb, Henrik
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Rorsman, Patrik, ...
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Sörhede Winzell, ...
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Endocrinology
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University of Gothenburg
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