E-cadherin interactions regulate β-cell proliferation in islet-like structures

Islet function is dependent on cells within the islet interacting with each other. E- cadherin ( ECAD) mediates Ca2+- dependent homophilic cell adhesion between b- cells within islets and has been identified as a tumour suppressor. We generated clones of the MIN6 beta- cell line that stably over- ( S) and under-express ( alpha S) ECAD. Modified expression of ECAD was confirmed by quantitative RT- PCR, immunoblotting and immunocytochemistry. Preproinsulin mRNA, insulin content and basal rates of insulin secretion were higher in S cells compared to aS and control ( V) cells. However, stimulated insulin secretory responses were unaffected by ECAD expression levels. ECAD expression did affect proliferation, with enhanced ECAD expression being associated with reduced proliferation and vice versa. Formation of islet- like structures was associated with a significant reduction in proliferation of V and S cells but not aS cells. These data suggest that ECAD expression levels do not modulate insulin secretory function but are consistent with a role for ECAD in the regulation of beta-cell proliferation.