PMID- 29481838
OWN - NLM
STAT- MEDLINE
DCOM- 20190423
LR  - 20190423
IS  - 1089-8638 (Electronic)
IS  - 0022-2836 (Linking)
VI  - 430
IP  - 7
DP  - 2018 Mar 30
TI  - mTORC2 Signaling: A Path for Pancreatic beta Cell's Growth and Function.
PG  - 904-918
LID - S0022-2836(18)30086-X [pii]
LID - 10.1016/j.jmb.2018.02.013 [doi]
AB  - The mechanistic target of rapamycin (mTOR) signaling pathway is an evolutionary 
      conserved pathway that senses signals from nutrients and growth factors to 
      regulate cell growth, metabolism and survival. mTOR acts in two biochemically and 
      functionally distinct complexes, mTOR complex 1 (mTORC1) and 2 (mTORC2), which 
      differ in terms of regulatory mechanisms, substrate specificity and functional 
      outputs. While mTORC1 signaling has been extensively studied in islet/beta-cell 
      biology, recent findings demonstrate a distinct role for mTORC2 in the regulation 
      of pancreatic beta-cell function and mass. mTORC2, a key component of the growth 
      factor receptor signaling, is declined in beta cells under diabetogenic conditions 
      and in pancreatic islets from patients with type 2 diabetes. beta cell-selective 
      mTORC2 inactivation leads to glucose intolerance and acceleration of diabetes as 
      a result of reduced beta-cell mass, proliferation and impaired glucose-stimulated 
      insulin secretion. Thereby, many mTORC2 targets, such as AKT, PKC, FOXO1, MST1 
      and cell cycle regulators, play an important role in beta-cell survival and 
      function. This indicates mTORC2 as important pathway for the maintenance of 
      beta-cell homeostasis, particularly to sustain proper beta-cell compensatory response 
      in the presence of nutrient overload and metabolic demand. This review summarizes 
      recent emerging advances on the contribution of mTORC2 and its associated 
      signaling on the regulation of glucose metabolism and functional beta-cell mass 
      under physiological and pathophysiological conditions in type 2 diabetes.
CI  - Copyright (c) 2018 Elsevier Ltd. All rights reserved.
FAU - Yuan, Ting
AU  - Yuan T
AD  - University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen, 
      Germany.
FAU - Lupse, Blaz
AU  - Lupse B
AD  - University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen, 
      Germany.
FAU - Maedler, Kathrin
AU  - Maedler K
AD  - University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen, 
      Germany.
FAU - Ardestani, Amin
AU  - Ardestani A
AD  - University of Bremen, Centre for Biomolecular Interactions Bremen, Bremen, 
      Germany. Electronic address: ardestani.amin@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20180223
PL  - Netherlands
TA  - J Mol Biol
JT  - Journal of molecular biology
JID - 2985088R
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 2)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Insulin-Secreting Cells/*metabolism
MH  - Intercellular Signaling Peptides and Proteins/physiology
MH  - Islets of Langerhans/growth & development
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Mechanistic Target of Rapamycin Complex 2/*metabolism
MH  - *Signal Transduction
OTO - NOTNLM
OT  - diabetes
OT  - insulin secretion
OT  - mTOR
OT  - mTORC2
OT  - beta cell
EDAT- 2018/02/27 06:00
MHDA- 2019/04/24 06:00
CRDT- 2018/02/27 06:00
PHST- 2017/12/05 00:00 [received]
PHST- 2018/02/14 00:00 [revised]
PHST- 2018/02/14 00:00 [accepted]
PHST- 2018/02/27 06:00 [pubmed]
PHST- 2019/04/24 06:00 [medline]
PHST- 2018/02/27 06:00 [entrez]
AID - S0022-2836(18)30086-X [pii]
AID - 10.1016/j.jmb.2018.02.013 [doi]
PST - ppublish
SO  - J Mol Biol. 2018 Mar 30;430(7):904-918. doi: 10.1016/j.jmb.2018.02.013. Epub 2018 
      Feb 23.