Nutrition Research Reviews
- Nutrition Research Reviews (2003), 16 : pp 253-266
- Copyright © The Authors 2003
Research Article
Recent advances in physiological and pathological significance of NAD+ metabolites: roles of poly(ADP-ribose) and cyclic ADP-ribose in insulin secretion and diabetogenesis
Hiroshi Okamotoa1 c1 and Shin Takasawaa1
a1 Department of Biochemistry and Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories) Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Abstract
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.
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Correspondence:
c1 *Corresponding author: Dr Hiroshi Okamoto, fax +81 227178083, email okamotoh@mail.tains.tohoku.ac.jp
