PMID- 20965146
OWN - NLM
STAT- MEDLINE
DCOM- 20110208
LR  - 20131121
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 505
IP  - 2
DP  - 2011 Jan 15
TI  - Supplement of TCA cycle intermediates protects against high 
      glucose/palmitate-induced INS-1 beta cell death.
PG  - 231-41
LID - 10.1016/j.abb.2010.10.011 [doi]
AB  - The aim of this study is to investigate the effect of mitochondrial metabolism on 
      high glucose/palmitate (HG/PA)-induced INS-1 beta cell death. Long-term treatment 
      of INS-1 cells with HG/PA impaired energy-producing metabolism accompanying with 
      depletion of TCA cycle intermediates. Whereas an inhibitor of carnitine palmitoyl 
      transferase 1 augmented HG/PA-induced INS-1 cell death, stimulators of fatty acid 
      oxidation protected the cells against the HG/PA-induced death. Furthermore, 
      whereas mitochondrial pyruvate carboxylase inhibitor phenylacetic acid augmented 
      HG/PA-induced INS-1 cell death, supplementation of TCA cycle metabolites 
      including leucine/glutamine, methyl succinate/alpha-ketoisocaproic acid, dimethyl 
      malate, and valeric acid or treatment with a glutamate dehydrogenase activator, 
      aminobicyclo-heptane-2-carboxylic acid (BCH), significantly protected the cells 
      against the HG/PA-induced death. In particular, the mitochondrial tricarboxylate 
      carrier inhibitor, benzene tricarboxylate (BTA), also showed a strong protective 
      effect on the HG/PA-induced INS-1 cell death. Knockdown of glutamate 
      dehydrogenase or tricarboxylate carrier augmented or reduced the HG/PA-induced 
      INS-1 cell death, respectively. Both BCH and BTA restored HG/PA-induced reduction 
      of energy metabolism as well as depletion of TCA intermediates. These data 
      suggest that depletion of the TCA cycle intermediate pool and impaired 
      energy-producing metabolism may play a role in HG/PA-induced cytotoxicity to beta 
      cells and thus, HG/PA-induced beta cell glucolipotoxicity can be protected by 
      nutritional or pharmacological maneuver enhancing anaplerosis or reducing 
      cataplerosis.
CI  - Copyright A(c) 2010 Elsevier Inc. All rights reserved.
FAU - Choi, Sung-E
AU  - Choi SE
AD  - Institute for Medical Sciences, Ajou University School of Medicine, Suwon, 
      Republic of Korea.
FAU - Lee, Youn-Jung
AU  - Lee YJ
FAU - Hwang, Geum-Sook
AU  - Hwang GS
FAU - Chung, Joo Hee
AU  - Chung JH
FAU - Lee, Soo-Jin
AU  - Lee SJ
FAU - Lee, Ji-Hyun
AU  - Lee JH
FAU - Han, Seung Jin
AU  - Han SJ
FAU - Kim, Hae Jin
AU  - Kim HJ
FAU - Lee, Kwan-Woo
AU  - Lee KW
FAU - Kim, Youngsoo
AU  - Kim Y
FAU - Jun, Hee-Sook
AU  - Jun HS
FAU - Kang, Yup
AU  - Kang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20101018
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Benzene Derivatives)
RN  - 0 (Carboxylic Acids)
RN  - 0 (Carrier Proteins)
RN  - 0 (Palmitates)
RN  - 0 (Tricarboxylic Acids)
RN  - 0 (citrate-binding transport protein)
RN  - 569-51-7 (benzene 1,2,3-tricarboxylic acid)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 1.4.1.2 (Glutamate Dehydrogenase)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Benzene Derivatives/pharmacology
MH  - Carboxylic Acids/pharmacology
MH  - Carrier Proteins/genetics
MH  - Cell Death/*drug effects
MH  - Cell Line, Tumor
MH  - *Citric Acid Cycle/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Energy Metabolism/drug effects
MH  - Gene Knockdown Techniques
MH  - Glucose/metabolism/*toxicity
MH  - Glutamate Dehydrogenase/deficiency/genetics
MH  - Insulin-Secreting Cells/*cytology/*drug effects/metabolism
MH  - Mitochondria/drug effects/metabolism
MH  - Oxidation-Reduction/drug effects
MH  - Palmitates/metabolism/*toxicity
MH  - Rats
MH  - Tricarboxylic Acids/pharmacology
EDAT- 2010/10/23 06:00
MHDA- 2011/02/09 06:00
CRDT- 2010/10/23 06:00
PHST- 2010/08/25 00:00 [received]
PHST- 2010/10/12 00:00 [revised]
PHST- 2010/10/14 00:00 [accepted]
PHST- 2010/10/23 06:00 [entrez]
PHST- 2010/10/23 06:00 [pubmed]
PHST- 2011/02/09 06:00 [medline]
AID - S0003-9861(10)00439-X [pii]
AID - 10.1016/j.abb.2010.10.011 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2011 Jan 15;505(2):231-41. doi: 10.1016/j.abb.2010.10.011. 
      Epub 2010 Oct 18.