PMID- 21099326
OWN - NLM
STAT- MEDLINE
DCOM- 20110516
LR  - 20190516
IS  - 1938-2022 (Electronic)
IS  - 1938-2014 (Linking)
VI  - 2
IP  - 5
DP  - 2010 Sep-Oct
TI  - Mitochondrial proteome analysis reveals altered expression of voltage dependent 
      anion channels in pancreatic beta-cells exposed to high glucose.
PG  - 283-92
AB  - Chronic hyperglycemia leads to deterioration of insulin release from pancreatic 
      beta-cells as well as insulin action on peripheral tissues. However, the mechanism 
      underlying beta-cell dysfunction resulting from glucose toxicity has not been fully 
      elucidated. The aim of the present study was to define a set of alterations in 
      mitochondrial protein profiles of pancreatic beta-cell line in response to 
      glucotoxic condition using 2-DE and tandem mass spectrometry. INS1E cells were 
      incubated in the presence of 5.5 and 20 mM glucose for 72 hrs and mitochondria 
      were isolated. Approximately 75 protein spots displayed significant changes (p < 
      0.05) in relative abundance in the presence of 20 mM glucose compared to 
      controls. Mitochondrial proteins down regulated under glucotoxic conditions 
      includes ATP synthase alpha chain and delta chain, malate dehydrogenase, aconitase, 
      trifunctional enzyme beta subunit, NADH cytochrome b5 reductase and 
      voltage-dependent anion-selective channel protein (VDAC) 2. VDAC1, 75 kDa 
      glucose-regulated protein, heat shock protein (HSP) 60 and HSP10 were found to be 
      upregulated. The orchestrated changes in expression of VDACs and multiple other 
      proteins involved in nutrient metabolism, ATP synthesis, cellular defense, 
      glycoprotein folding and mitochondrial DNA stability may explain cellular 
      dysfunction in glucotoxicity resulting in altered insulin secretion.
FAU - Ahmed, Meftun
AU  - Ahmed M
AD  - The Oxford Centre for Diabetes, Endocrinology & Metabolism, Oxford University, 
      Oxford, UK. meftun@hotmail.com
FAU - Muhammed, Sarheed J
AU  - Muhammed SJ
FAU - Kessler, Benedikt
AU  - Kessler B
FAU - Salehi, Albert
AU  - Salehi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100901
PL  - United States
TA  - Islets
JT  - Islets
JID - 101495366
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Peptides)
RN  - 0 (Proteome)
RN  - 0 (VDAC1 protein, human)
RN  - 0 (VDAC2 protein, human)
RN  - 0 (Voltage-Dependent Anion Channel 2)
RN  - 0 (Voltage-Dependent Anion Channels)
RN  - EC 1.6.- (Voltage-Dependent Anion Channel 1)
SB  - IM
MH  - Cell Line
MH  - *Down-Regulation
MH  - Electrophoresis, Gel, Two-Dimensional
MH  - Humans
MH  - Hydrolysis
MH  - *Hyperglycemia
MH  - Insulin-Secreting Cells/*metabolism
MH  - Mitochondrial Proteins/*metabolism
MH  - Peptides/chemistry/metabolism
MH  - Proteome/*metabolism
MH  - Spectrometry, Mass, Electrospray Ionization
MH  - Tandem Mass Spectrometry
MH  - *Up-Regulation
MH  - Voltage-Dependent Anion Channel 1/metabolism
MH  - Voltage-Dependent Anion Channel 2/metabolism
MH  - Voltage-Dependent Anion Channels/*metabolism
EDAT- 2010/11/26 06:00
MHDA- 2011/05/17 06:00
CRDT- 2010/11/25 06:00
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2011/05/17 06:00 [medline]
AID - 12639 [pii]
AID - 10.4161/isl.2.5.12639 [doi]
PST - ppublish
SO  - Islets. 2010 Sep-Oct;2(5):283-92. doi: 10.4161/isl.2.5.12639. Epub 2010 Sep 1.