Cadherin engagement improves insulin secretion of single human ß-cells.
Diabetes
; 64(3): 887-96, 2015 Mar.
Article
en En
| MEDLINE
| ID: mdl-25277393
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 ß-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 ß-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 ß-cells compared with round ß-cells. Furthermore, cadherin-mediated adhesion induced an asymmetric distribution of cortical actin in ß-cells. Our results demonstrate that adhesion of ß-cells to E- and N-cadherins is regulated by insulin secretagogues and that E- and N-cadherin engagement promotes stimulated insulin secretion.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cadherinas
/
Células Secretoras de Insulina
/
Insulina
Límite:
Humans
Idioma:
En
Revista:
Diabetes
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza