Recent advances in the Okamoto model: The CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in β-cells

Hiroshi Okamoto, Shin Takasawa

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

Twenty years ago, we first proposed our hypothesis on β-cell damage and its prevention (the Okamoto model), according to which poly(ADP-ribose) synthetase/polymerase (PARP) activation is critically involved in the consumption of NAD+, leading to energy depletion and cell death by necrosis. Recently, the model was reconfirmed by results using PARP knockout mice and has been recognized as providing the basis for necrotic death of various cells and tissues. Based on the model, we proposed two signal systems in β-cells: one is the CD38-cyclic ADP-ribose (cADPR) signal system for insulin secretion, and the other is the regenerating gene protein (Reg)-Reg receptor system for β-cell regeneration. The physiological and pathological significance of the two signal systems in a variety of cells and tissues as well as in pancreatic β-cells has recently been recognized. Here, we describe the Okamoto model and its descendents, the CD38-cADPR signal system and the Reg-Reg receptor system, focusing on recent advances and how their significance came to light. Because PARP is involved in Reg gene transcription to induce β-cell regeneration, and the PARP activation reduces the cellular NAD+ to decrease the formation of cADPR (a second messenger for insulin secretion) and further to cause necrotic β-cell death, PARP and its inhibitors have key roles in the induction of β-cell regeneration, the maintenance of insulin secretion, and the prevention of β-cell death.

Original languageEnglish
Pages (from-to)S462-S473
JournalDiabetes
Volume51
Issue numberSUPPL. 3
DOIs
Publication statusPublished - 2002 Dec 1

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Recent advances in the Okamoto model: The CD38-cyclic ADP-ribose signal system and the regenerating gene protein (Reg)-Reg receptor system in β-cells'. Together they form a unique fingerprint.

Cite this