PMID- 18834443
OWN - NLM
STAT- MEDLINE
DCOM- 20081209
LR  - 20211203
IS  - 1463-1326 (Electronic)
IS  - 1462-8902 (Linking)
VI  - 10 Suppl 4
DP  - 2008 Nov
TI  - The role of mTOR in the adaptation and failure of beta-cells in type 2 diabetes.
PG  - 157-69
LID - 10.1111/j.1463-1326.2008.00952.x [doi]
AB  - Mammalian target of rapamycin (mTOR) is an important nutrient sensor that plays a 
      critical role in cellular metabolism, growth, proliferation and apoptosis and in 
      the cellular response to oxidative stress. In addition, mTOR-raptor complex, also 
      called mammalian target of rapamycin complex 1 (mTORC1), generates an inhibitory 
      feedback loop on insulin receptor substrate proteins. It was suggested that 
      nutrient overload leads to insulin/insulin-like growth factor 1 resistance in 
      peripheral insulin-responsive tissues and in the beta-cells through sustained 
      activation of mTORC1. In this review, we summarize the literature on the 
      regulation and function of mTOR, its role in the organism's response to nutrients 
      and its potential impact on lifespan, insulin resistance and the metabolic 
      adaptation to hyperglycaemia in type 2 diabetes. We also propose a hypothesis 
      based on data in the literature as well as data generated in our laboratory, 
      which assigns a central positive role to mTOR in the maintenance of beta-cell 
      function and mass in the diabetic environment.
FAU - Leibowitz, G
AU  - Leibowitz G
AD  - Endocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew 
      University Medical Center, Jerusalem, Israel. gleib@hadassah.org.il
FAU - Cerasi, E
AU  - Cerasi E
FAU - Ketzinel-Gilad, M
AU  - Ketzinel-Gilad M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - England
TA  - Diabetes Obes Metab
JT  - Diabetes, obesity & metabolism
JID - 100883645
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis/physiology
MH  - Diabetes Mellitus, Type 2/*metabolism/physiopathology
MH  - Female
MH  - Humans
MH  - Hyperglycemia/*physiopathology
MH  - Insulin-Like Growth Factor I/metabolism
MH  - Insulin-Secreting Cells/metabolism
MH  - Male
MH  - Mice
MH  - Obesity/*metabolism/physiopathology
MH  - Oxidative Stress
MH  - Protein Kinases/*physiology
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases
RF  - 99
EDAT- 2008/10/18 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/10/18 09:00
PHST- 2008/10/18 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/18 09:00 [entrez]
AID - DOM952 [pii]
AID - 10.1111/j.1463-1326.2008.00952.x [doi]
PST - ppublish
SO  - Diabetes Obes Metab. 2008 Nov;10 Suppl 4:157-69. doi: 
      10.1111/j.1463-1326.2008.00952.x.