PMID- 22110477
OWN - NLM
STAT- MEDLINE
DCOM- 20120325
LR  - 20220318
IS  - 1687-5303 (Electronic)
IS  - 1687-5214 (Print)
IS  - 1687-5214 (Linking)
VI  - 2012
DP  - 2012
TI  - Mitochondrial dysfunction and beta-cell failure in type 2 diabetes mellitus.
PG  - 703538
LID - 10.1155/2012/703538 [doi]
LID - 703538
AB  - Type 2 diabetes mellitus (T2DM) is the most common human endocrine disease and is 
      characterized by peripheral insulin resistance and pancreatic islet beta-cell 
      failure. Accumulating evidence indicates that mitochondrial dysfunction is a 
      central contributor to beta-cell failure in the evolution of T2DM. As reviewed 
      elsewhere, reactive oxygen species (ROS) produced by beta-cell mitochondria as a 
      result of metabolic stress activate several stress-response pathways. This paper 
      focuses on mechanisms whereby ROS affect mitochondrial structure and function and 
      lead to beta-cell failure. ROS activate UCP2, which results in proton leak across 
      the mitochondrial inner membrane, and this leads to reduced beta-cell ATP synthesis 
      and content, which is a critical parameter in regulating glucose-stimulated 
      insulin secretion. In addition, ROS oxidize polyunsaturated fatty acids in 
      mitochondrial cardiolipin and other phospholipids, and this impairs membrane 
      integrity and leads to cytochrome c release into cytosol and apoptosis. Group VIA 
      phospholipase A(2) (iPLA(2)beta) appears to be a component of a mechanism for repairing 
      mitochondrial phospholipids that contain oxidized fatty acid substituents, and 
      genetic or acquired iPLA(2)beta-deficiency increases beta-cell mitochondrial 
      susceptibility to injury from ROS and predisposes to developing T2DM. 
      Interventions that attenuate ROS effects on beta-cell mitochondrial phospholipids 
      might prevent or retard development of T2DM.
FAU - Ma, Zhongmin Alex
AU  - Ma ZA
AD  - Division of Experimental Diabetes and Aging, Department of Geriatrics and 
      Palliative Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA. 
      zhongmin.ma@mssm.edu
FAU - Zhao, Zhengshan
AU  - Zhao Z
FAU - Turk, John
AU  - Turk J
LA  - eng
GR  - R01 NS063962/NS/NINDS NIH HHS/United States
GR  - R37 DK034388/DK/NIDDK NIH HHS/United States
GR  - P30 DK056341/DK/NIDDK NIH HHS/United States
GR  - R37-DK34388/DK/NIDDK NIH HHS/United States
GR  - P60 DK020579/DK/NIDDK NIH HHS/United States
GR  - P30 DK020579/DK/NIDDK NIH HHS/United States
GR  - P41 RR000954/RR/NCRR NIH HHS/United States
GR  - P30 DK056341-11/DK/NIDDK NIH HHS/United States
GR  - R01-NS063962/NS/NINDS NIH HHS/United States
GR  - P60-DK20579/DK/NIDDK NIH HHS/United States
GR  - P41-RR00954/RR/NCRR NIH HHS/United States
GR  - P30-DK56341/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
DEP - 20111109
PL  - United States
TA  - Exp Diabetes Res
JT  - Experimental diabetes research
JID - 101274844
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Ion Channels)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Phospholipids)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (UCP2 protein, human)
RN  - 0 (Uncoupling Protein 2)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.1.1.4 (Group IV Phospholipases A2)
SB  - IM
MH  - Adenosine Triphosphate/biosynthesis
MH  - Apoptosis
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Fatty Acids, Unsaturated/chemistry
MH  - Group IV Phospholipases A2/deficiency/physiology
MH  - Humans
MH  - Insulin Resistance
MH  - Insulin-Secreting Cells/*physiology
MH  - Ion Channels/physiology
MH  - Lipid Peroxidation
MH  - Mitochondria/*physiology
MH  - Mitochondrial Membranes/physiology
MH  - Mitochondrial Proteins/physiology
MH  - Oxidation-Reduction
MH  - Phospholipids/chemistry
MH  - Reactive Oxygen Species/metabolism
MH  - Uncoupling Protein 2
PMC - PMC3216264
EDAT- 2011/11/24 06:00
MHDA- 2012/03/27 06:00
PMCR- 2011/11/09
CRDT- 2011/11/24 06:00
PHST- 2011/07/20 00:00 [received]
PHST- 2011/09/03 00:00 [accepted]
PHST- 2011/11/24 06:00 [entrez]
PHST- 2011/11/24 06:00 [pubmed]
PHST- 2012/03/27 06:00 [medline]
PHST- 2011/11/09 00:00 [pmc-release]
AID - 10.1155/2012/703538 [doi]
PST - ppublish
SO  - Exp Diabetes Res. 2012;2012:703538. doi: 10.1155/2012/703538. Epub 2011 Nov 9.