PMID- 22611253
OWN - NLM
STAT- MEDLINE
DCOM- 20130927
LR  - 20220331
IS  - 1759-4685 (Electronic)
IS  - 1759-4685 (Linking)
VI  - 4
IP  - 4
DP  - 2012 Aug
TI  - Age- and diet-dependent requirement of DJ-1 for glucose homeostasis in mice with 
      implications for human type 2 diabetes.
PG  - 221-30
LID - 10.1093/jmcb/mjs025 [doi]
AB  - Elderly patients often suffer from multiple age-related diseases. Here we show 
      that the expression of DJ-1, an antioxidant protein with reduced expression in 
      the central nervous system of patients with Parkinson's disease, is reduced in 
      pancreatic islets of patients with type 2 diabetes mellitus (T2DM). In contrast, 
      under non-diabetic conditions, DJ-1 expression increases in mouse and human 
      islets during aging. In mouse islets, we show that DJ-1 prevents an increase in 
      reactive oxygen species levels as the mice age. This antioxidant function 
      preserves mitochondrial integrity and physiology, prerequisites for 
      glucose-stimulated insulin secretion. Accordingly, DJ-1-deficient mice develop 
      glucose intolerance and reduced beta cell area as they age or gain weight. Our data 
      suggest that DJ-1 is more generally involved in age- and lifestyle-related human 
      diseases and show for the first time that DJ-1 plays a key role in glucose 
      homeostasis and might serve as a novel drug target for T2DM.
FAU - Jain, Deepak
AU  - Jain D
AD  - Institute of Metabolic Physiology, Heinrich-Heine University, D-40225 Dusseldorf, 
      Germany.
FAU - Jain, Ruchi
AU  - Jain R
FAU - Eberhard, Daniel
AU  - Eberhard D
FAU - Eglinger, Jan
AU  - Eglinger J
FAU - Bugliani, Marco
AU  - Bugliani M
FAU - Piemonti, Lorenzo
AU  - Piemonti L
FAU - Marchetti, Piero
AU  - Marchetti P
FAU - Lammert, Eckhard
AU  - Lammert E
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120519
PL  - United States
TA  - J Mol Cell Biol
JT  - Journal of molecular cell biology
JID - 101503669
RN  - 0 (Insulin)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Oncogene Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.11.1.15 (Peroxiredoxins)
RN  - EC 3.1.2.- (PARK7 protein, human)
RN  - EC 3.1.2.- (PARK7 protein, mouse)
RN  - EC 3.1.2.- (Protein Deglycase DJ-1)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/drug effects/*metabolism
MH  - Animals
MH  - Diabetes Mellitus, Type 2/complications/*metabolism
MH  - *Diet
MH  - Glucose/*metabolism/pharmacology
MH  - Glucose Intolerance/complications/metabolism
MH  - *Homeostasis/drug effects
MH  - Humans
MH  - Insulin/metabolism
MH  - Insulin Secretion
MH  - Insulinoma/metabolism/pathology
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Islets of Langerhans/drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Mitochondria/metabolism
MH  - Oncogene Proteins/*metabolism
MH  - Peroxiredoxins
MH  - Protein Deglycase DJ-1
MH  - Reactive Oxygen Species/metabolism
MH  - Up-Regulation/drug effects
EDAT- 2012/05/23 06:00
MHDA- 2013/09/28 06:00
CRDT- 2012/05/22 06:00
PHST- 2012/05/22 06:00 [entrez]
PHST- 2012/05/23 06:00 [pubmed]
PHST- 2013/09/28 06:00 [medline]
AID - mjs025 [pii]
AID - 10.1093/jmcb/mjs025 [doi]
PST - ppublish
SO  - J Mol Cell Biol. 2012 Aug;4(4):221-30. doi: 10.1093/jmcb/mjs025. Epub 2012 May 
      19.