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Cadherin Engagement Improves Insulin Secretion of Single Human β-Cells

Published in Diabetes. 2015, vol. 64, no. 3, p. 887-96
Abstract The aim of this study was to assess whether cadherin-mediated adhesion of human islet cells was affected by insulin secretagogues and explore the role of cadherins in the secretory activity of β-cells. Experiments were carried out with single islet cells adherent to chimeric proteins made of functional E-, N-, or P-cadherin ectodomains fused to the Fc fragment of immunoglobulin (E-cad/Fc, N-cad/Fc, and P-cad/Fc) and immobilized on an inert substrate. We observed that cadherin expression in islet cells was not affected by insulin secretagogues. Adhesion tests showed that islet cells attached to N-cad/Fc and E-cad/Fc acquired, in a time- and secretagogue-dependent manner, a spreading form that was inhibited by blocking cadherin antibodies. By reverse hemolytic plaque assay, we showed that glucose-stimulated insulin secretion of single β-cells was increased by N-cad/Fc and E-cad/Fc adhesion compared with control. In the presence of E-cad/Fc and after glucose stimulation, we showed that total insulin secretion was six times higher in spreading β-cells compared with round β-cells. Furthermore, cadherin-mediated adhesion induced an asymmetric distribution of cortical actin in β-cells. Our results demonstrate that adhesion of β-cells to E- and N-cadherins is regulated by insulin secretagogues and that E- and N-cadherin engagement promotes stimulated insulin secretion.
PMID: 25277393
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PARNAUD, Géraldine et al. Cadherin Engagement Improves Insulin Secretion of Single Human β-Cells. In: Diabetes, 2015, vol. 64, n° 3, p. 887-96. doi: 10.2337/db14-0257 https://archive-ouverte.unige.ch/unige:48166

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Deposited on : 2015-03-12

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