PMID- 8013761
OWN - NLM
STAT- MEDLINE
DCOM- 19940725
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 43
IP  - 7
DP  - 1994 Jul
TI  - Hepatocyte growth factor/scatter factor has insulinotropic activity in human 
      fetal pancreatic cells.
PG  - 947-53
AB  - Fetal mesenchyme-derived factors are likely to play an important role in 
      pancreatic islet development and growth. We have used primary cultures of human 
      fetal pancreatic tissue to identify growth factors that have morphogenic, 
      mitogenic, and insulinotropic activity. The formation of islet-like cell clusters 
      (ICCs) during a 6-day culture was stimulated two- to threefold by hepatocyte 
      growth factor/scatter factor (HGF/SF) basic fibroblast growth factor (FGF)-2, and 
      to a lesser extent by keratinocyte growth factor (FGF-7) and insulin-like growth 
      factor-II (IGF-II). In contrast, transforming growth factor-beta (TGF-beta) had a 
      strong inhibitory effect. The ICCs formed during HGF/SF stimulation consisted 
      mainly of epithelial cells, whereas FGF-2-induced ICCs were predominantly 
      nonepithelial. Furthermore, although both FGF-2 and HGF/SF increased the total 
      insulin content of the cultures, only HGF/SF increased the insulin content per 
      DNA. Quantitatively, HGF/SF stimulated a 2.3-fold increase in the proportion of 
      insulin-positive cells and a 3-fold higher number of replicating beta-cells. 
      Blocking of the IGF-I receptor inhibited ICC formation but did not affect their 
      insulin content. Immunoneutralizing TGF-beta resulted in increased cell growth 
      and insulin content, indicating the presence of an endogenous inhibitory TGF-beta 
      activity in the model system. Our results suggest that HGF/SF may be an important 
      component of the fetal mesenchyme-derived factors responsible for pancreatic 
      islet development. HGF/SF also may prove valuable for supporting the in vitro 
      growth of islet cells.
FAU - Otonkoski, T
AU  - Otonkoski T
AD  - Lucy Thorne Whittier Children's Center, La Jolla, California.
FAU - Beattie, G M
AU  - Beattie GM
FAU - Rubin, J S
AU  - Rubin JS
FAU - Lopez, A D
AU  - Lopez AD
FAU - Baird, A
AU  - Baird A
FAU - Hayek, A
AU  - Hayek A
LA  - eng
GR  - DK-18811/DK/NIDDK NIH HHS/United States
GR  - R01-DK-39087/DK/NIDDK 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  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Antibodies)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Growth Substances)
RN  - 0 (Insulin)
RN  - 0 (Transforming Growth Factor beta)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - VC2W18DGKR (Thymidine)
SB  - IM
MH  - Abortion, Legal
MH  - Analysis of Variance
MH  - Antibodies/pharmacology
MH  - Antibodies, Monoclonal/pharmacology
MH  - Cell Division/drug effects
MH  - Cells, Cultured
MH  - DNA/biosynthesis/metabolism
MH  - Female
MH  - Fetus
MH  - Gestational Age
MH  - Growth Substances/*pharmacology
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Insulin/*metabolism
MH  - Islets of Langerhans/drug effects/embryology/*physiology
MH  - Pancreas/cytology/drug effects/*embryology
MH  - Pregnancy
MH  - Receptor, IGF Type 1/immunology/physiology
MH  - Thymidine/metabolism
MH  - Transforming Growth Factor beta/immunology/physiology
EDAT- 1994/07/01 00:00
MHDA- 1994/07/01 00:01
CRDT- 1994/07/01 00:00
PHST- 1994/07/01 00:00 [pubmed]
PHST- 1994/07/01 00:01 [medline]
PHST- 1994/07/01 00:00 [entrez]
AID - 10.2337/diab.43.7.947 [doi]
PST - ppublish
SO  - Diabetes. 1994 Jul;43(7):947-53. doi: 10.2337/diab.43.7.947.