PMID- 23562377
OWN - NLM
STAT- MEDLINE
DCOM- 20130816
LR  - 20131121
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 535
IP  - 2
DP  - 2013 Jul 15
TI  - Protective effect of nicotinamide on high glucose/palmitate-induced 
      glucolipotoxicity to INS-1 beta cells is attributed to its inhibitory activity to 
      sirtuins.
PG  - 187-96
LID - S0003-9861(13)00099-4 [pii]
LID - 10.1016/j.abb.2013.03.011 [doi]
AB  - This study was initiated to determine whether the protective effect of 
      nicotinamide (NAM) on high glucose/palmitate (HG/PA)-induced INS-1 beta cell 
      death was due to its role as an anti-oxidant, nicotinamide dinucleotide (NAD+) 
      precursor, or inhibitor of NAD+-consuming enzymes such as poly (ADP-ribose) 
      polymerase (PARP) or sirtuins. All anti-oxidants tested were not protective 
      against HG/PA-induced INS-1 cell death. Direct supplementation of NAD+ or 
      indirect supplementation through NAD+ salvage or de novo pathway did not protect 
      the death. Knockdown of the NAD+ salvage pathway enzymes such as nicotinamide 
      phosphoribosyl transferase (NAMPT) or nicotinamide mononucleotide 
      adenyltransferase (NMNAT) did not augment death. On the other hand, 
      pharmacological inhibition or knockdown of PARP did not affect death. However, 
      sirtinol as an inhibitor of NAD-dependant deacetylase or knockdown of SIRT3 or 
      SIRT4 significantly reduced the HG/PA-induced death. These data suggest that 
      protective effect of NAM on beta cell glucolipotoxicity is attributed to its 
      inhibitory activity on sirtuins.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Lee, Soo-Jin
AU  - Lee SJ
AD  - Institute for Medical Sciences, Ajou University School of Medicine, Suwon, 
      Republic of Korea.
FAU - Choi, Sung-E
AU  - Choi SE
FAU - Jung, Ik-Rak
AU  - Jung IR
FAU - Lee, Kwan-Woo
AU  - Lee KW
FAU - Kang, Yup
AU  - Kang Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130403
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (Antioxidants)
RN  - 0 (Ephrin-B2)
RN  - 0 (Palmitates)
RN  - 0U46U6E8UK (NAD)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 25X51I8RD4 (Niacinamide)
RN  - 26656-46-2 (Poly Adenosine Diphosphate Ribose)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
RN  - EC 3.5.1.- (SIRT5 protein, rat)
RN  - EC 3.5.1.- (Sirtuin 3)
RN  - EC 3.5.1.- (Sirtuins)
RN  - GAN16C9B8O (Glutathione)
RN  - IY9XDZ35W2 (Glucose)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Cell Death/drug effects
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Ephrin-B2/metabolism
MH  - Gene Knockdown Techniques
MH  - Glucose/*metabolism/toxicity
MH  - Glutathione/pharmacology
MH  - Insulin-Secreting Cells/cytology/*drug effects
MH  - MAP Kinase Kinase 4/metabolism
MH  - NAD/metabolism/pharmacology
MH  - Niacinamide/*pharmacology
MH  - Palmitates/*metabolism/toxicity
MH  - Phosphorylation
MH  - Poly Adenosine Diphosphate Ribose/antagonists & inhibitors
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Sirtuin 3/antagonists & inhibitors/genetics/metabolism
MH  - Sirtuins/*antagonists & inhibitors/genetics/metabolism
MH  - Transcription Factor CHOP/metabolism
EDAT- 2013/04/09 06:00
MHDA- 2013/08/21 06:00
CRDT- 2013/04/09 06:00
PHST- 2012/12/06 00:00 [received]
PHST- 2013/03/14 00:00 [revised]
PHST- 2013/03/17 00:00 [accepted]
PHST- 2013/04/09 06:00 [entrez]
PHST- 2013/04/09 06:00 [pubmed]
PHST- 2013/08/21 06:00 [medline]
AID - S0003-9861(13)00099-4 [pii]
AID - 10.1016/j.abb.2013.03.011 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2013 Jul 15;535(2):187-96. doi: 10.1016/j.abb.2013.03.011. 
      Epub 2013 Apr 3.