title: The expression and function of glucose-dependent insulinotropic polypeptide in the embryonic mouse pancreas.
abstract: OBJECTIVE
  Glucose-dependent insulinotropic polypeptide (GIP) is a member of a structurally related group of hormones that also includes glucagon, glucagon-like peptides, and secretin. GIP is an incretin, known to modulate glucose-induced insulin secretion. Recent studies have shown that glucagon is necessary for early insulin-positive differentiation, and a similar role for incretins in regulating embryonic insulin-positive differentiation seems probable. Here we studied the role of GIP signaling in insulin-positive differentiation in the embryonic mouse pancreas.
  
  
  METHODS
  The ontogeny of the GIP ligand and GIP receptor in the embryonic pancreas was investigated by immunohistochemistry and RT-PCR. GIP signaling was inhibited in cultured embryonic pancreata using morpholine-ring antisense against GIP ligand and receptor, or small interfering RNA (siRNA) for GIP ligand and receptor. Markers of endocrine cells and their progenitors were studied by immunohistochemistry and RT-PCR.
  
  
  RESULTS
  GIP and GIP receptor mRNA were both detected in the embryonic pancreas by embryonic day 9.5 and then persisted throughout gestation. GIP was generally coexpressed with glucagon by immunostaining. The GIP receptor was typically coexpressed with insulin. Morpholine-ring antisense or siRNA against either GIP ligand or GIP receptor both inhibited the differentiation of insulin-positive cells. Inhibition of GIP or its receptor also led to a decrease in the number of Pdx-1-positive and sox9-positive cells in the cultured embryonic pancreas. The number of Pax6- and Nkx2.2-positive cells, representative of developing pancreatic endocrine cells and β-cells, respectively, was also decreased.
  
  
  CONCLUSIONS
  GIP signaling may play a role in early embryonic pancreas differentiation to form insulin-positive cells or β-cells.
authors.affiliation: Division of Pediatric General and Thoracic Surgery, Children's Hospital, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
authors.forename: Krishna
authors.initials: K
authors.lastname: Prasadan
authors.forename: Masayuki
authors.initials: M
authors.lastname: Koizumi
authors.forename: Sidhartha
authors.initials: S
authors.lastname: Tulachan
authors.forename: Chiyo
authors.initials: C
authors.lastname: Shiota
authors.forename: Nikesh
authors.initials: N
authors.lastname: Lath
authors.forename: Jose
authors.initials: J
authors.lastname: Paredes
authors.forename: Ping
authors.initials: P
authors.lastname: Guo
authors.forename: Yousef
authors.initials: Y
authors.lastname: El-Gohary
authors.forename: Marcus
authors.initials: M
authors.lastname: Malek
authors.forename: Sohail
authors.initials: S
authors.lastname: Shah
authors.forename: George K
authors.initials: GK
authors.lastname: Gittes
mesh_terms: D000818:Animals; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism*; D000090322:Homeobox Protein Nkx-2.2; D007150:Immunohistochemistry; D051379:Mice; D009924:Organ Culture Techniques; D010179:Pancreas / Q000196:embryology / Q000378:metabolism*; D034741:RNA, Small Interfering; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D000090322:Homeobox Protein Nkx-2.2; C000715627:Nkx2-2 protein, mouse; D034741:RNA, Small Interfering; D011964:Receptors, Gastrointestinal Hormone; D005749:Gastric Inhibitory Polypeptide; C041086:gastric inhibitory polypeptide receptor