PMID- 11145583
OWN - NLM
STAT- MEDLINE
DCOM- 20010301
LR  - 20211203
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 142
IP  - 1
DP  - 2001 Jan
TI  - Phosphatidylinositol-3,4,5-trisphosphate is required for insulin-like growth 
      factor 1-mediated survival of 3T3-L1 preadipocytes.
PG  - 205-12
AB  - Adipocyte number, a determinant of adipose tissue mass, reflects the balance 
      between the rates of proliferation/differentiation vs. apoptosis of 
      preadipocytes. The percentage of 3T3-L1 preadipocytes undergoing cell death 
      following serum deprivation was reduced by 10 nM insulin-like growth factor 
      (IGF)-1 (from 50.0 +/- 0.7% for control starved cells to 27.5 +/- 3.1%). TUNEL 
      staining confirmed the apoptotic nature of the cell death. The protective effect 
      of IGF-1 was blocked by phosphoinositide 3-kinase (PI3K) inhibitors, wortmannin, 
      and LY294002, but was unaffected by rapamycin, PD98059, or SB203580, which 
      inhibit mammalian target of rapamycin (mTOR), ERK kinase (MEK1), and p38 MAPK 
      respectively. Exogenous PI(3,4,5)P3 (10 microM), the principal product of 
      IGF-1-stimulated PI3K in 3T3-L1 preadipocytes, had a modest survival effect on 
      its own, reducing cell death from 47.9 +/- 3.4% to 35.6 +/- 3.5%. When added to 
      the combination of IGF-1 and LY294002, PI(3,4,5)P3 reversed most of the 
      inhibitory effect of LY294002 on IGF-1-dependent cell survival, protein kinase 
      B/Akt phosphorylation, and caspase-3 activity. Taken together, these results 
      implicate PI(3,4,5)P3 as a necessary signal for the anti-apoptotic action of 
      IGF-1 on 3T3-L1 preadipocytes.
FAU - Gagnon, A
AU  - Gagnon A
AD  - The Departments of Medicine and Biochemistry, Microbiology & Immunology, Loeb 
      Health Research Institute, Ottawa Hospital, University of Ottawa, Ottawa, Canada.
FAU - Dods, P
AU  - Dods P
FAU - Roustan-Delatour, N
AU  - Roustan-Delatour N
FAU - Chen, C S
AU  - Chen CS
FAU - Sorisky, A
AU  - Sorisky A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Androstadienes)
RN  - 0 (Chromones)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Imidazoles)
RN  - 0 (Morpholines)
RN  - 0 (Phosphatidylinositol Phosphates)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Pyridines)
RN  - 0 (phosphatidylinositol 3,4,5-triphosphate)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - OU13V1EYWQ (SB 203580)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
RN  - W36ZG6FT64 (Sirolimus)
RN  - XVA4O219QW (Wortmannin)
SB  - IM
MH  - 3T3 Cells
MH  - Adipocytes/*cytology/drug effects
MH  - Androstadienes/pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Chromones/pharmacology
MH  - Culture Media, Serum-Free
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Imidazoles/pharmacology
MH  - In Situ Nick-End Labeling
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - MAP Kinase Kinase 1
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol Phosphates/*metabolism/pharmacology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Serine-Threonine Kinases/antagonists & inhibitors
MH  - Pyridines/pharmacology
MH  - Sirolimus/pharmacology
MH  - Wortmannin
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2001/01/06 11:00
MHDA- 2001/03/07 10:01
CRDT- 2001/01/06 11:00
PHST- 2001/01/06 11:00 [pubmed]
PHST- 2001/03/07 10:01 [medline]
PHST- 2001/01/06 11:00 [entrez]
AID - 10.1210/endo.142.1.7902 [doi]
PST - ppublish
SO  - Endocrinology. 2001 Jan;142(1):205-12. doi: 10.1210/endo.142.1.7902.