In rodents and humans, the rate of beta cell proliferation declines rapidly after birth; formation of the islets of Langerhans begins perinatally and continues after birth.

We tested whether increased levels of E-cadherin during islet formation mediate the decline in beta cell proliferation rate by contributing to a reduction of molecules that mediate cell replication. In vitro, a cultured beta cell line formed into clusters resembling an islet displayed increased E-cadherin but decreased nuclear β-catenin and cyclin D2 (cell division molecules) , and reduced rates of cell proliferation, compared with monolayers.

Reduction of E-cadherin increased cell proliferation and levels of cyclins D1 and D2.

After birth, beta cells showed increased levels of E-cadherin, but decreased levels of D-cyclin, whereas islets of mice in which the E-cadherin gene had been knocked out showed increased levels of D-cyclins and nuclear β-catenin, as well as increased beta cell proliferation. These islets were significantly larger than those of control mice . Interestingly, these changes correlated with reduced insulin response to ambient glucose, both in vitro and in vivo.

The findings support our hypothesis by indicating an important role of E-cadherin in the control of beta cell mass and function.