J Korean Diabetes Assoc.  2004 Feb;28(1):20-27.

Activin A Converts Pancreatic Ductal Cells into Insulin-Secreting Cells

• Lee KH
• Park MK
• Kang HW
• Kim HJ
• Jeong IK
• Yoo HJ
• Jeong JH
• Min YK
• Lee MS
• Kim KW
• Lee MK

Abstract

BACKGROUND: Islet transplantation as a potential treatment for diabetes has been investigated extensively over the past years. One of the major limitations to successful islet transplantation is shortage of insulin-producing tissue, which has stimulated the search for alternative sources, and recently, attention has been focused on the possible use of controlled differentiation of stem cells to obtain specialized cells useful in treating many diseases. It is currently believed that pancreatic progenitor or stem cells exist in the ductal cell population. Activin A is a member of the TGFbeta superfamily, which can block the exocrine pancreatic development and potentiate the endocrine development of the pancreas. In this study, whether activin A could expand and/or differentiate the ductal cells into insulin-producing cells was examined.
METHODS
From a collagenase P digested pancreas, ductal tissue was cultured under conditions that allowed expansion as a monolayer, where the cells were overlaid with a rat tail collagen I-coated dish. Activin A cDNA was transfected into rat ductal cells by using Lipofectamine, and the insulin secretion, content and differentiation markers examined. RESULT: The clumps of ductal tissue adhered to the dish 24 hr later, and formed a complete monolayer after 3 days of culture. Activin A overexpression significantly increased both the insulin secretion and content from the ductal cells. The glucose(16.7mM)-induced insulin secretion was also significantly increased. Immunohistochemistry and RT-PCR analyses revealed expression of PDX-1, as well as insulin & GLUT2.
CONCLUSION
Activin A overexpression could potentiate the differentiation of pancreatic ductal cells, which might provide a potential new source of cinsulin- producing cells for transplantation

Keyword

Ductal cells; Activin A; PDX-1; GLUT2; Differentiation

MeSH Terms

Activins*
Animals
Antigens, Differentiation
Collagen
Collagenases
DNA, Complementary
Immunohistochemistry
Insulin
Insulin-Secreting Cells*
Islets of Langerhans Transplantation
Pancreas
Pancreatic Ducts*
Rats
Stem Cells
Tail
Transforming Growth Factor beta
Activins
Antigens, Differentiation
Collagen
Collagenases
DNA, Complementary
Insulin
Transforming Growth Factor beta