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 Okamoto, Shin Takasawa

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)253-266
Number of pages14
JournalNutrition Research Reviews
Volume16
Issue number2
DOIs
Publication statusPublished - 2003 Dec

Keywords

  • Apoptosis
  • Necrosis
  • Okamoto model for β-cell damage
  • Poly(ADP-ribose) synthetase/polymerase
  • Regenerating gene

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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