PMID- 8770939
OWN - NLM
STAT- MEDLINE
DCOM- 19961010
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 137
IP  - 7
DP  - 1996 Jul
TI  - A role for hepatocyte growth factor/scatter factor in fetal mesenchyme-induced 
      pancreatic beta-cell growth.
PG  - 3131-9
AB  - We have investigated the role of hepatocyte growth factor/scatter factor (HGF/SF) 
      in the growth and/or differentiation of pancreatic islet beta-cells. We found 
      that in the human fetal pancreas immunoreactive HGF/SF receptor (c-met 
      proto-oncogene product) is preferentially associated with the developing 
      beta-cells. In the adult pancreas, c-met messenger RNA is highly enriched in the 
      islets and the immunoreactive protein is also restricted to the islet beta-cells. 
      HGF/SF messenger RNA content of fetal pancreas-derived fibroblasts is more than 
      10-fold higher than that of adult fibroblasts. Culture of human fetal pancreatic 
      epithelial cells in conditioned medium from the fetal pancreatic fibroblasts 
      caused a 2.4-fold stimulation of the formation of islet-like cell clusters that 
      was due to both mitogenic and morphogenic effects. Beta-cell proliferation in the 
      cell clusters was stimulated 3.5-fold by the conditioned medium, and this was 
      associated with a marked decrease in insulin content. All of the effects of the 
      conditioned medium were blocked by anti-HGF/SF antibody. Specificity was 
      confirmed by overriding the blocking effect of the antibody with excess 
      recombinant HGF/SF. Conditioned medium from adult pancreatic fibroblasts 
      stimulated islet-like cell cluster formation only slightly, and did not affect 
      beta-cell replication. These results suggest that HGF/SF secreted by fetal 
      fibroblasts is mitogenic to beta-cells. Taken together, our findings indicate an 
      important role for HGF/SF in fetal mesenchyme-induced pancreatic beta-cell 
      growth.
FAU - Otonkoski, T
AU  - Otonkoski T
AD  - The Whittier Institute, Department of Pediatrics, University of California San 
      Diego, La Jolla, 92037.
FAU - Cirulli, V
AU  - Cirulli V
FAU - Beattie, M
AU  - Beattie M
FAU - Mally, M I
AU  - Mally MI
FAU - Soto, G
AU  - Soto G
FAU - Rubin, J S
AU  - Rubin JS
FAU - Hayek, A
AU  - Hayek A
LA  - eng
GR  - 2SO6 GM-47165-05/GM/NIGMS NIH HHS/United States
GR  - R01-DK 39087/DK/NIDDK NIH HHS/United States
GR  - RR-04050/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Insulin)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-92-5 (Glucagon)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adult
MH  - Analysis of Variance
MH  - Cell Division
MH  - Cells, Cultured
MH  - Culture Media, Conditioned
MH  - Fetus
MH  - Fibroblasts/cytology/physiology
MH  - Fluorescent Antibody Technique
MH  - Gestational Age
MH  - Glucagon/analysis/biosynthesis
MH  - Hepatocyte Growth Factor/biosynthesis/*pharmacology/*physiology
MH  - Humans
MH  - Insulin/analysis/biosynthesis
MH  - Islets of Langerhans/cytology/embryology/*physiology
MH  - Mesoderm/*physiology
MH  - Microscopy, Confocal
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins c-met
MH  - RNA, Messenger/biosynthesis
MH  - Receptor Protein-Tyrosine Kinases/*biosynthesis
MH  - Recombinant Proteins/pharmacology
MH  - Transcription, Genetic
EDAT- 1996/07/01 00:00
MHDA- 1996/07/01 00:01
CRDT- 1996/07/01 00:00
PHST- 1996/07/01 00:00 [pubmed]
PHST- 1996/07/01 00:01 [medline]
PHST- 1996/07/01 00:00 [entrez]
AID - 10.1210/endo.137.7.8770939 [doi]
PST - ppublish
SO  - Endocrinology. 1996 Jul;137(7):3131-9. doi: 10.1210/endo.137.7.8770939.