E-cadherin and cell adhesion: a role in architecture and function in the pancreatic islet.
OBJECTIVE
The efficient secretion of insulin from beta-cells requires extensive intra-islet communication. The cell surface adhesion protein epithelial (E)-cadherin (ECAD) establishes and maintains epithelial tissues such as the islets of Langerhans. In this study, the role of ECAD in regulating insulin secretion from pseudoislets was investigated.


METHODS
The effect of an immuno-neutralising ECAD on gross morphology, cytosolic calcium signalling, direct cell-to-cell communication and insulin secretion was assessed by fura-2 microfluorimetry, Lucifer Yellow dye injection and insulin ELISA in an insulin-secreting model system.


RESULTS
Antibody blockade of ECAD reduces glucose-evoked changes in [Ca(2+)](i) and insulin secretion. Neutralisation of ECAD causes a breakdown in the glucose-stimulated synchronicity of calcium oscillations between discrete regions within the pseudoislet, and the transfer of dye from an individual cell within a cell cluster is attenuated in the absence of ECAD ligation, demonstrating that gap junction communication is disrupted. The functional consequence of neutralising ECAD is a significant reduction in insulin secretion.


CONCLUSIONS
Cell adhesion via ECAD has distinct roles in the regulation of intercellular communication between beta-cells within islets, with potential repercussions for insulin secretion.
Rogers
Gareth J
GJ
Molecular Physiology Group, Biomedical Research Institute, Department of Biological Sciences, University of Warwick Coventry, UK.
Hodgkin
Matthew N
MN
Squires
Paul E
PE
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D005502:Food; D017629:Gap Junctions / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D009500:Neutralization Tests; D051381:Rats
D000906:Antibodies; D015820:Cadherins; D007328:Insulin; D005947:Glucose