title: Cadherin engagement improves insulin secretion of single human β-cells.
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.
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland geraldine.parnaud@unige.ch.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Parnaud
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Lavallard
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Benoît
authors.initials: B
authors.lastname: Bedat
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Matthey-Doret
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morel
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Thierry
authors.initials: T
authors.lastname: Berney
authors.affiliation: Department of Surgery, Cell Isolation and Transplantation Center, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Domenico
authors.initials: D
authors.lastname: Bosco
mesh_terms: D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
chemical_list: D015820:Cadherins; D007328:Insulin; D005947:Glucose