title: Glucagon is required for early insulin-positive differentiation in the developing mouse pancreas.
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 ( approximately 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.
authors.affiliation: Laboratory of Surgical Organogenesis, Children's Mercy Hospital, Kansas City, Missouri 64108, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.forename: Erica
authors.initials: E
authors.lastname: Daume
authors.forename: Barry
authors.initials: B
authors.lastname: Preuett
authors.forename: Troy
authors.initials: T
authors.lastname: Spilde
authors.forename: Amina
authors.initials: A
authors.lastname: Bhatia
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Mark
authors.initials: M
authors.lastname: Hembree
authors.forename: Pradip
authors.initials: P
authors.lastname: Manna
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
mesh_terms: D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D017931:DNA Primers; D005314:Embryonic and Fetal Development; D005260:Female; D005865:Gestational Age; D005934:Glucagon / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000196:embryology*; D051379:Mice; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000196:embryology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D052336:Proglucagon; D011498:Protein Precursors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D007328:Insulin; D020319:Oligodeoxyribonucleotides, Antisense; D011498:Protein Precursors; D052336:Proglucagon; D005934:Glucagon