A role for activin A and betacellulin in human fetal pancreatic cell differentiation and growth

Activin A (Act.A), a member of the transforming growth factor beta family o f secreted proteins, has been implicated in the regulation of growth and di fferentiation of various cell types. Betacellulin (BTC), a member of the ep idermal growth factor family, converts exocrine AR42J cells to insulin-expr essing cells when combined with Act.A. We have used primary cultures of hum an fetal pancreatic tissue to identify the effects of Act.A and/or ETC on i slet development and growth. Exposure to Act.A resulted in a 1.5-fold incre ase in insulin content (P < 0.005) and a 2-fold increase in the number of c ells immunopositive for insulin (P < 0.005). The formation of islet-like ce ll clusters, containing mainly epithelial cells, during a Ei-day culture, w as stimulated 1.4-fold by ETC (P < 0.05). ETC alone caused a 2.6-fold incre ase in DNA synthesis (P < 0.005). These data suggest that Act.A induces end ocrine differentiation, whereas BTC has a mitogenic effect on human undiffe rentiated pancreatic epithelial cells.