EGF receptor in pancreatic beta-cell mass regulation.
Pancreatic islet development is impaired in mice lacking EGFRs (epidermal growth factor receptors). Even partial tissue-specific attenuation of EGFR signalling in the islets leads to markedly reduced beta-cell proliferation and development of diabetes during the first weeks after birth. Out of the many EGFR ligands, betacellulin has been specifically associated with positive effects on beta-cell growth, through both increased proliferation and neogenesis. EGFR action is also necessary for the beta-cell mitogenic activity of the gut hormone GLP-1 (glucagon-like peptide 1). Finally, in vitro models demonstrate a central role for EGFR in transdifferentiation of pancreatic acinar and ductal cells into endocrine islet cells. EGFR thus plays an essential role in beta-cell mass regulation, but its mechanisms of action remain poorly understood.
Miettinen
Päivi
P
Hospital for Children and Adolescents and the Biomedicum Stem Cell Center, University of Helsinki, 00014 Helsinki, Finland.
Ormio
Päivi
P
Hakonen
Elina
E
Banerjee
Meenal
M
Otonkoski
Timo
T
D000818:Animals; D049109:Cell Proliferation; D054338:Cell Transdifferentiation; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000201:enzymology*; D008024:Ligands; D015398:Signal Transduction
D008024:Ligands; D066246:ErbB Receptors