Figure 8. Model of AP-stimulated β-cell proliferation.

(a) In the presense of high glucose, beta cells increase intracellular Ca²⁺ levels leading to activation of calcineurin (CN). CN dephosphorylates NFATc proteins such as NFATc1 leading to nuclear import. Previous studies demonstrated a critical role for the CN–NFATc pathway in the regulation of β-cell proliferation. Nuclear NFATc kinases Dyrk1a and Gsk3b phosphorylate NFATc proteins leading to nuclear export. AP compounds, such as GNF4877, inhibit Dyrk1a and Gsk3b leading to blockade of NFATc nuclear export and increased β-cell proliferation.