Human β-Cell Proliferation and Intracellular Signaling Part 2: Still Driving in the Dark Without a Road Map

Bernal-Mizrachi, ErnestoKulkarni, RohitScott, Donald K.Mauvais-Jarvis, FranckStewart, Andrew F.Garcia-Ocaña, Adolfo2015-04-012014Bernal-Mizrachi, Ernesto, Rohit N. Kulkarni, Donald K. Scott, Franck Mauvais-Jarvis, Andrew F. Stewart, and Adolfo Garcia-Ocaña. 2014. “Human β-Cell Proliferation and Intracellular Signaling Part 2: Still Driving in the Dark Without a Road Map.” Diabetes 63 (3): 819-831. doi:10.2337/db13-1146. http://dx.doi.org/10.2337/db13-1146.0012-1797http://nrs.harvard.edu/urn-3:HUL.InstRepos:14351360Enhancing β-cell proliferation is a major goal for type 1 and type 2 diabetes research. Unraveling the network of β-cell intracellular signaling pathways that promote β-cell replication can provide the tools to address this important task. In a previous Perspectives in Diabetes article, we discussed what was known regarding several important intracellular signaling pathways in rodent β-cells, including the insulin receptor substrate/phosphatidylinositol-3 kinase/Akt (IRS-PI3K-Akt) pathways, glycogen synthase kinase-3 (GSK3) and mammalian target of rapamycin (mTOR) S6 kinase pathways, protein kinase Cζ (PKCζ) pathways, and their downstream cell-cycle molecular targets, and contrasted that ample knowledge to the small amount of complementary data on human β-cell intracellular signaling pathways. In this Perspectives, we summarize additional important information on signaling pathways activated by nutrients, such as glucose; growth factors, such as epidermal growth factor, platelet-derived growth factor, and Wnt; and hormones, such as leptin, estrogen, and progesterone, that are linked to rodent and human β-cell proliferation. With these two Perspectives, we attempt to construct a brief summary of knowledge for β-cell researchers on mitogenic signaling pathways and to emphasize how little is known regarding intracellular events linked to human β-cell replication. This is a critical aspect in the long-term goal of expanding human β-cells for the prevention and/or cure of type 1 and type 2 diabetes.en-USHuman β-Cell Proliferation and Intracellular Signaling Part 2: Still Driving in the Dark Without a Road MapJournal Article2015-04-0110.2337/db13-1146