Synergistic Effects of Activin A and Fibroblast Growth Factor 2 in the Modulation of Insulin Expression1

Diabetes is the most prevalent and serious metabolic disease, and the number of diabetic patients worldwide is increasing. The reduction of insulin biosynthes is in pancreatic β-cells is closely associated with the onset and progression of diabetes, therefore, it is important to search for ways to induce insulin-producing cells in non-β-cells. In the present study, it has been reported that activin A and a basic fibroblast growth factor 2 (FGF2), can synergistically increase the insulin mRNA level, in both mouse E14 striatal primary cell cultures and the hippocampal neuronal cell line HT22. Activin A and FGF2 can jointly stimulate the nuclear translocation of Smad3 and specifically activate ERK1/2. It is interesting to note that a specific inhibitor for MEK, U0126, can efficiently block the induction of an insulin promoter activity by activin A and FGF2. This indicates that activin A collaborates with FGF2, giving a signal to induce the insulin gene through selective activation of the ERK-type MAP kinase and Smad3 in mouse striatal and HT22 cells. These data suggest that activin A may act in concert with FGF2 for the development of insulin -positive neurons.