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Diabetes 51:3229-3236, 2002
© 2002 by the American Diabetes Association, Inc.

Glucagon Is Required for Early Insulin-Positive Differentiation in the Developing Mouse Pancreas

Krishna Prasadan, Erica Daume, Barry Preuett, Troy Spilde, Amina Bhatia, Hiroyuki Kobayashi, Mark Hembree, Pradip Manna, and George K. Gittes

From the Laboratory of Surgical Organogenesis, Children’s Mercy Hospital, Kansas City, Missouri

The embryonic pancreas is thought to develop from pluripotent endodermal cells that give rise to endocrine and exocrine cells. A key guidance mechanism for pancreatic development has previously been found to be epithelial-mesenchymal interaction. Interactions within the epithelium, however, have not been well studied. Glucagon is the earliest peptide hormone present at appreciable levels in the developing pancreatic epithelium (embryonic day [E]-9.5 in mouse). Insulin accumulation begins slightly later (E11 in mouse), followed by a rapid accumulation during the "second wave" of insulin differentiation (~E15). Here we found that blocking early expression and function of glucagon, but not GLP-1, an alternate gene product of preproglucagon mRNA, prevented insulin-positive differentiation in early embryonic (E11) pancreas. These results suggest a novel concept and a key role for glucagon in the paracrine induction of differentiation of other pancreatic components in the early embryonic pancreas.



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