TY - JOUR
T1 - Recent advances in physiological and pathological significance of NAD + metabolites
T2 - Roles of poly(ADP-ribose) and cyclic ADP-ribose in insulin secretion and diabetogenesis
AU - Okamoto, Hiroshi
AU - Takasawa, Shin
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/12
Y1 - 2003/12
N2 - Poly(ADP-ribose) synthetase/polymerase (PARP) activation causes NAD + depletion in pancreatic β-cells, which results in necrotic cell death. On the other hand, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (CD38) synthesizes cyclic ADP-ribose from NAD+, which acts as a second messenger, mobilizing intracellular Ca2+ for insulin secretion in response to glucose in β-cells. PARP also acts as a regenerating gene (Reg) transcription factor to induce β-cell regeneration. This provides the new concept that NAD+ metabolism can control the cellular function through gene expression. Clinically, PARP could be one of the most important therapeutic targets; PARP inhibitors prevent cell death, maintain the formation of a second messenger, cyclic ADP-ribose, to achieve cell function, and keep PARP functional as a transcription factor for cell regeneration.
AB - Poly(ADP-ribose) synthetase/polymerase (PARP) activation causes NAD + depletion in pancreatic β-cells, which results in necrotic cell death. On the other hand, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (CD38) synthesizes cyclic ADP-ribose from NAD+, which acts as a second messenger, mobilizing intracellular Ca2+ for insulin secretion in response to glucose in β-cells. PARP also acts as a regenerating gene (Reg) transcription factor to induce β-cell regeneration. This provides the new concept that NAD+ metabolism can control the cellular function through gene expression. Clinically, PARP could be one of the most important therapeutic targets; PARP inhibitors prevent cell death, maintain the formation of a second messenger, cyclic ADP-ribose, to achieve cell function, and keep PARP functional as a transcription factor for cell regeneration.
KW - Apoptosis
KW - Necrosis
KW - Okamoto model for β-cell damage
KW - Poly(ADP-ribose) synthetase/polymerase
KW - Regenerating gene
UR - http://www.scopus.com/inward/record.url?scp=0347086141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0347086141&partnerID=8YFLogxK
U2 - 10.1079/NRR200362
DO - 10.1079/NRR200362
M3 - Review article
C2 - 19087393
AN - SCOPUS:0347086141
VL - 16
SP - 253
EP - 266
JO - Nutrition Research Reviews
JF - Nutrition Research Reviews
SN - 0954-4224
IS - 2
ER -