Rhee, MarieLee, Seung-HwanKim, Ji-WonHam, Dong-SikPark, Heon-SeokYang, Hae KyungShin, Ju-YoungCho, Jae-HyoungKim, Young-BumYoun, Byung-SooSul, Hei SookYoon, Kun-Ho2016-05-022016Rhee, M., S. Lee, J. Kim, D. Ham, H. Park, H. K. Yang, J. Shin, et al. 2016. “Preadipocyte factor 1 induces pancreatic ductal cell differentiation into insulin-producing cells.” Scientific Reports 6 (1): 23960. doi:10.1038/srep23960. http://dx.doi.org/10.1038/srep23960.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:26860107The preadipocyte factor 1 (Pref-1) is involved in the proliferation and differentiation of various precursor cells. However, the intracellular signaling pathways that control these processes and the role of Pref-1 in the pancreas remain poorly understood. Here, we showed that Pref-1 induces insulin synthesis and secretion via two independent pathways. The overexpression of Pref-1 activated MAPK signaling, which induced nucleocytoplasmic translocation of FOXO1 and PDX1 and led to the differentiation of human pancreatic ductal cells into β-like cells and an increase in insulin synthesis. Concurrently, Pref-1 activated Akt signaling and facilitated insulin secretion. A proteomics analysis identified the Rab43 GTPase-activating protein as a downstream target of Akt. A serial activation of both proteins induced various granular protein syntheses which led to enhanced glucose-stimulated insulin secretion. In a pancreatectomised diabetic animal model, exogenous Pref-1 improved glucose homeostasis by accelerating pancreatic ductal and β-cell regeneration after injury. These data establish a novel role for Pref-1, opening the possibility of applying this molecule to the treatment of diabetes.en-USJournal Article2016-05-0210.1038/srep23960