题名：Defective prolactin signaling impairs pancreatic beta-cell development during the perinatal period.
作者：AUFFRET J; FREEMARK M; CARRE N; MATHIEU Y; TOURREL-CUZIN C; LOMBES M; MOVASSAT J; BINART N;
来源：Am J Physiol Endocrinol Metab. 2013 Nov;305(10):E1309-18. doi: [ IF= 0.00 ] ]
摘要：Prolactin (PRL) and placental lactogens stimulate beta-cell replication and
insulin production in pancreatic islets and insulinoma cells through binding to
the PRL receptor (PRLR). However, the contribution of PRLR signaling to beta-cell
ontogeny and function in perinatal life and the effects of the lactogens on
adaptive islet growth are poorly understood. We provide evidence that expansion
of beta-cell mass during both embryogenesis and the postnatal period is impaired
in the PRLR(-/-) mouse model. PRLR(-/-) newborns display a 30% reduction of
beta-cell mass, consistent with reduced proliferation index at E18.5. PRL
stimulates leucine incorporation and S6 kinase phosphorylation in INS-1 cells,
supporting a role for beta-cell mTOR signaling in PRL action. Interestingly, a
defect in the development of acini is also observed in absence of PRLR signaling,
with a sharp decline in cellular size in both endocrine and exocrine
compartments. Of note, a decrease in levels of IGF-II, a PRL target, in the
Goto-Kakizaki (GK) rat, a spontaneous model of type 2 diabetes, is associated
with a lack of PRL-mediated beta-cell proliferation in embryonic pancreatic buds.
Reduced pancreatic IGF-II expression in both rat and mouse models suggests that
this factor may constitute a molecular link between PRL signaling and cell
ontogenesis. Together, these results provide evidence that PRL signaling is
essential for pancreas ontogenesis during the critical perinatal window
responsible for establishing functional beta-cell reserve.