Fig. 7.

Relationships among INSM1, Menin and Cyclin D1 during islet development. This diagram summarizes results from our data, which show that in young islets INSM1 is localized in the nucleus and Menin expression is low. Localization of INSM1 in the nucleus causes an increase in Cyclin D1 transcription, which promotes cell cycle activation and proliferation. In adult islets, Menin expression increases, causing INSM1 to localize in the cytoplasm and bind to Cyclin D1, arresting the cell cycle and halting proliferation. Thus, loss of MEN1 in mature islets reverses the cell cycle arrest caused by INSM1 translocation to the cytoplasm, resulting in islet proliferation.