Betacellulin inhibits amylase and glucagon production and promotes beta cell differentiation in mouse embryonic pancreas.
OBJECTIVE
Betacellulin, a member of the epidermal growth factor family, is expressed in the pancreas and is thought to regulate differentiation of beta cells during development. The aim of the present study was to investigate the effects of exogenous betacellulin on the development of the mouse embryonic pancreas.


METHODS
We used an in vitro culture model system based on the isolation and culture of the dorsal embryonic pancreas from day 11.5 embryos. Cultures were treated for up to 10 days with 10 ng/ml betacellulin and then analysed for changes in the expression of pancreatic exocrine, endocrine and ductal markers.


RESULTS
Pancreases developed in culture and expressed the full complement of exocrine (both acinar and ductal) and endocrine cell types. Betacellulin enhanced branching morphogenesis and the proliferation of mesenchyme, increased Pdx1 and insulin production and inhibited the production of the exocrine cell marker amylase and the endocrine hormone glucagon.


CONCLUSIONS
These results suggest betacellulin has distinct and separate effects on exocrine, endocrine and ductal differentiation. In the future, betacellulin could perhaps be utilised to increase the production of beta cells from embryonic pancreatic tissue for therapeutic transplantation.
Thowfeequ
S
S
Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Bath, UK.
Ralphs
K L
KL
Yu
W-Y
WY
Slack
J M W
JM
Tosh
D
D
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D066259:Betacellulin; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D054439:Ghrelin / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism*; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D051379:Mice; D010179:Pancreas / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010191:Pancreatic Polypeptide / Q000378:metabolism; D013004:Somatostatin / Q000378:metabolism
D066259:Betacellulin; C587852:Btc protein, mouse; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D000681:Amylases