PMID- 21465524
OWN - NLM
STAT- MEDLINE
DCOM- 20110720
LR  - 20211203
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 112
IP  - 5
DP  - 2011 May
TI  - Metformin sensitizes insulin signaling through AMPK-mediated PTEN down-regulation 
      in preadipocyte 3T3-L1 cells.
PG  - 1259-67
LID - 10.1002/jcb.23000 [doi]
AB  - Insulin resistance is the primary cause responsible for type 2 diabetes. 
      Phosphatase and tensin homolog (PTEN) plays a negative role in insulin signaling 
      and its inhibition improves insulin sensitivity. Metformin is a widely used 
      insulin-sensitizing drug; however, the mechanism by which metformin acts is 
      poorly understood. To gain insight into the role of PTEN, we examined the effect 
      of metformin on PTEN expression. Metformin suppressed the expression of PTEN in 
      an AMP-activated protein kinase (AMPK)-dependent manner in preadipocyte 3T3-L1 
      cells. Knock-down of PTEN potentiated the increase in insulin-mediated 
      phosphorylation of Akt/ERK. Metformin also increased the phosphorylation of c-Jun 
      N-terminal kinase (JNK)-c-Jun and mammalian target of rapamycin (mTOR)-p70S6 
      kinase pathways. Both pharmacologic inhibition and knock-down of AMPK blocked 
      metformin-induced phosphorylation of JNK and mTOR. Knock-down of AMPK recovered 
      the metformin-induced PTEN down-regulation, suggesting the involvement of AMPK in 
      PTEN regulation. PTEN promoter activity was suppressed by metformin and 
      inhibition of mTOR and JNK by pharmacologic inhibitors blocked metformin-induced 
      PTEN promoter activity suppression. These findings provide evidence for a novel 
      role of AMPK on PTEN expression and thus suggest a possible mechanism by which 
      metformin may contribute to its beneficial effects on insulin signaling.
CI  - Copyright (c) 2010 Wiley-Liss, Inc.
FAU - Lee, Soo Kyung
AU  - Lee SK
AD  - Department of Anatomy, Korea University College of Medicine, Seoul, Korea.
FAU - Lee, Jung Ok
AU  - Lee JO
FAU - Kim, Ji Hae
AU  - Kim JH
FAU - Kim, Su Jin
AU  - Kim SJ
FAU - You, Ga Young
AU  - You GY
FAU - Moon, Ji Wook
AU  - Moon JW
FAU - Jung, Jin Hee
AU  - Jung JH
FAU - Park, Sun Hwa
AU  - Park SH
FAU - Uhm, Kyung-Ok
AU  - Uhm KO
FAU - Park, Ji Man
AU  - Park JM
FAU - Suh, Pann-Ghill
AU  - Suh PG
FAU - Kim, Hyeon Soo
AU  - Kim HS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - 3T3-L1 Cells
MH  - AMP-Activated Protein Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Adipocytes/metabolism
MH  - Animals
MH  - Diabetes Mellitus, Type 2/*drug therapy/genetics
MH  - Down-Regulation/drug effects
MH  - Glucose/metabolism
MH  - Hypoglycemic Agents/*pharmacology
MH  - Insulin/*metabolism
MH  - *Insulin Resistance
MH  - Metformin/*pharmacology
MH  - Mice
MH  - PTEN Phosphohydrolase/*metabolism
MH  - Phosphorylation/drug effects
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases
EDAT- 2011/04/06 06:00
MHDA- 2011/07/21 06:00
CRDT- 2011/04/06 06:00
PHST- 2011/04/06 06:00 [entrez]
PHST- 2011/04/06 06:00 [pubmed]
PHST- 2011/07/21 06:00 [medline]
AID - 10.1002/jcb.23000 [doi]
PST - ppublish
SO  - J Cell Biochem. 2011 May;112(5):1259-67. doi: 10.1002/jcb.23000.