title: Epidermal growth factor (EGF)-receptor signalling is needed for murine beta cell mass expansion in response to high-fat diet and pregnancy but not after pancreatic duct ligation.
abstract: OBJECTIVE
  Epidermal growth factor receptor (EGFR) signalling is essential for the proper fetal development of pancreatic islets and in the postnatal formation of an adequate beta cell mass. In this study we investigated the role of EGFR signalling in the physiological states of beta cell mass expansion in adults during metabolic syndrome and pregnancy, as well as in regeneration after pancreatic duct ligation.
  
  
  METHODS
  Heterozygous Pdx1-EGFR-dominant-negative (E1-DN) mice, which have a kinase-negative EGFR under the Pdx1 promoter, and wild-type mice were both subjected to a high-fat diet, pregnancy and pancreatic duct ligation.
  
  
  RESULTS
  The beta cell mass of wild-type mice fed the high-fat diet increased by 70% and the mice remained normoglycaemic; the E1-DN mice became diabetic and failed to show any compensatory beta cell mass expansion. Similarly, pregnant wild-type mice had four times more proliferating beta cells and a 75% increase in beta cell mass at mid-gestation, in contrast to the pregnant E1-DN mice, which did not show any significant beta cell compensation and were hyperglycaemic in an intraperitoneal glucose tolerance test. However, after pancreatic duct ligation, both the wild-type and E1-DN mice showed similar expression of Ngn3 (also known as Neurog3) and beta cell proliferation increased to a similar level in the ligated part of pancreas.
  
  
  CONCLUSIONS
  EGFR signalling is essential in beta cell mass expansion during a high-fat diet and pregnancy where replication is the primary mechanism for compensatory beta cell mass expansion. In contrast, EGFR signalling appears not to be crucial to increased beta cell proliferation after pancreatic duct ligation.
authors.affiliation: Research Programs Unit, Molecular Neurology, Biomedicum Stem Cell Centre, University of Helsinki, PO Box 63, (Haartmaninkatu 8), 00014 Helsinki, Finland. elina.hakonen@helsinki.fi
authors.forename: E
authors.initials: E
authors.lastname: Hakonen
authors.forename: J
authors.initials: J
authors.lastname: Ustinov
authors.forename: I
authors.initials: I
authors.lastname: Mathijs
authors.forename: J
authors.initials: J
authors.lastname: Palgi
authors.forename: L
authors.initials: L
authors.lastname: Bouwens
authors.forename: P J
authors.initials: PJ
authors.lastname: Miettinen
authors.forename: T
authors.initials: T
authors.lastname: Otonkoski
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology*; D008026:Ligation / Q000009:adverse effects*; D008297:Male; D051379:Mice; D010183:Pancreatic Ducts / Q000293:injuries*; D011247:Pregnancy; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D004041:Dietary Fats; D066246:ErbB Receptors