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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 10 3892-3897
Copyright © 2000 by The Endocrine Society


Original Studies

A Role for Activin A and Betacellulin in Human Fetal Pancreatic Cell Differentiation and Growth1

Carla Demeterco, Gillian M. Beattie, Sergio Atala Dib, Ana D. Lopez and Alberto Hayek

Whittier Institute and Department of Pediatrics (C.D., G.M.B., A.D.L., A.H.), University of California at San Diego, La Jolla, California 92037; and Federal University of Sao Paulo (C.D., S.A.D.), Sao Paulo, Brazil

Address correspondence and requests for reprints to: Dr. Alberto Hayek, The Islet Research Laboratory, Department of Pediatrics, University of California at San Diego, 9894 Genesee Avenue, La Jolla, California 92037. E-mail: ahayek{at}ucsd.edu

Activin A (Act.A), a member of the transforming growth factor ß family of secreted proteins, has been implicated in the regulation of growth and differentiation of various cell types. Betacellulin (BTC), a member of the epidermal growth factor family, converts exocrine AR42J cells to insulin-expressing cells when combined with Act.A. We have used primary cultures of human fetal pancreatic tissue to identify the effects of Act.A and/or BTC on islet development and growth. Exposure to Act.A resulted in a 1.5-fold increase in insulin content (P < 0.005) and a 2-fold increase in the number of cells immunopositive for insulin (P < 0.005). The formation of islet-like cell clusters, containing mainly epithelial cells, during a 5-day culture, was stimulated 1.4-fold by BTC (P < 0.05). BTC alone caused a 2.6-fold increase in DNA synthesis (P < 0.005). These data suggest that Act.A induces endocrine differentiation, whereas BTC has a mitogenic effect on human undifferentiated pancreatic epithelial cells.




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