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 - Funding Information:
The authors are grateful to Brent Bell for valuable assistance in preparing the manuscript. The studies are sup- ported in part by grants-in-aid from the Ministry of Education, Science, Sports, Culture, and Technology, Japan. All animal studies by the authors were conducted in accordance with guiding principles for the care and use of research animals promulgated by Tohoku University Graduate School of Medicine, Sendai, Japan.
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 -