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
Abstract
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.
Footnotes
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Address correspondence and reprint requests to George Gittes, Laboratory of Surgical Organogenesis, Children’s Mercy Hospital, 2401 Gillham St., HHC 623 C, Kansas City, MO 64108. E-mail: ggittes{at}cmh.edu.
Received for publication 2 November 2001 and accepted in revised form 2 August 2002.
ATG, adenine, thymine, guanine; DMEM, Dulbecco’s modified Eagle’s medium; FITC, fluorescein isothiocyanate; GLP-1, glucagon-like peptide-1.
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