RAPGEF4 and diabetes mellitus: Inactivation of both the PI3K-Akt and the Epac2/Rap1 signaling pathways appears highly relevant to the development of diabetes because the pathways have been reported to be essential for mediating survival, proliferation, glucose homeostasis, and lipid metabolism, among others (PI3K-Akt) [38] and for regulation of insulin granule dynamics by cAMP and insulin secretion (Epac2-Rap1) [39,40,41].