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Recent advances in physiological and pathological significance of NAD+ metabolites: roles of poly(ADP-ribose) and cyclic ADP-ribose in insulin secretion and diabetogenesis

Published online by Cambridge University Press:  14 December 2007

Hiroshi Okamoto  and
Shin Takasawa
Hiroshi Okamoto*
Affiliation:
Department of Biochemistry and Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories)Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
Shin Takasawa
Affiliation:
Department of Biochemistry and Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories)Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan
*
*Corresponding author: Dr Hiroshi Okamoto, fax +81 227178083, email okamotoh@mail.tains.tohoku.ac.jp
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Abstract

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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.

Keywords

Poly(ADP-ribose) synthetase/polymeraseOkamoto model for β-cell damageNecrosisApoptosisRegenerating gene
Type
Research Article
Information
Nutrition Research Reviews , Volume 16 , Issue 2 , December 2003 , pp. 253 - 266
Copyright
Copyright © The Authors 2003

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