FIGURE 2.

Mitogenic synergy in human beta cell proliferation. The figure presents how application of mitogens alone or in combinations influences the beta cell proliferation. Several of the most potent mitogenic compounds are depicted in the top block, together with the key signaling events through which they regulate beta cell proliferation (the block below). The bottom block of the figure demonstrates how the values of beta cell proliferation rates increase upon the application of dual or triple mitogen combinations in comparison to the effects of the individual mitogens. Numbers in brackets indicate the literature references. *For all the mitogens, except LIF, the values of proliferation rates were obtained with the staining for Ki67 presence, and are therefore suitable for comparison. For LIF the proliferation rate has been obtained with the EdU incorporation assay. LIF is included into the scheme as the first mitogen described in a triple combination (LIF + Harmine + TGF-beta inhibitor).