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Protective effect of nicotinamide on high glucose/palmitate-induced glucolipotoxicity to INS-1 beta cells is attributed to its inhibitory activity to sirtuins.

Lee, SJ; Choi, SE; Jung, IR; Lee, KW; Kang, Y
Archives of biochemistry and biophysics, 535(2):187-196, 2013
Journal Title
Archives of biochemistry and biophysics
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.
MeSH terms
Acetylcysteine/pharmacologyAnimalsAntioxidants/*pharmacologyCell Death/drug effectsCell Line, TumorCell Survival/drug effectsEphrin-B2/metabolismGene Knockdown TechniquesGlucose/*metabolism/toxicityGlutathione/pharmacologyInsulin-Secreting Cells/cytology/*drug effectsMAP Kinase Kinase 4/metabolismNAD/metabolism/pharmacologyNiacinamide/*pharmacologyPalmitates/*metabolism/toxicityPhosphorylationPoly Adenosine Diphosphate Ribose/antagonists & inhibitorsProto-Oncogene Proteins c-akt/metabolismRatsSirtuin 3/antagonists & inhibitors/genetics/metabolismSirtuins/*antagonists & inhibitors/genetics/metabolismTranscription Factor CHOP/metabolism
Appears in Collections:
Journal Papers > Research Organization > Chronic Inflammatory Disease Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Endocrinology & Metabolism
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
최, 성이이, 관우강, 엽
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