Supporting the role of CREB in promoting β-cell viability, in vivo studies show that transgenic expression of a dominant-negative CREB (A-CREB) in β-cells increases apoptosis and results in diabetes in mice [68], and in vitro studies demonstrate knockdown of CREB in INS-1 cells increased levels of cleaved caspase-3 [128]. This evidence concerns the gene CREB1 and diabetes mellitus.