Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular Ca<sup>2+</sup> mobilization and Reg (<b><i>Re</i></b><i>generating</i> <b><i>g</i></b><i>ene</i> protein)-Reg receptor system for cell regeneration
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- OKAMOTO Hiroshi
- Department of Biochemistry, Tohoku University Graduate School of Medicine Department of Biochemistry and Molecular Vascular Biology, Kanazawa University Graduate School of Medical Sciences
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- TAKASAWA Shin
- Department of Biochemistry, Nara Medical University
Bibliographic Information
- Other Title
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- Okamoto model for necrosis and its expansions, CD38-cyclic ADP-ribose signal system for intracellular Ca²⁺ mobilization and Reg (Regenerating gene protein)-Reg receptor system for cell regeneration
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Abstract
<p>In pancreatic islet cell culture models and animal models, we studied the molecular mechanisms involved in the development of insulin-dependent diabetes. The diabetogenic agents, alloxan and streptozotocin, caused DNA strand breaks, which in turn activated poly(ADP-ribose) polymerase/synthetase (PARP) to deplete NAD+, thereby inhibiting islet β-cell functions such as proinsulin synthesis and ultimately leading to β-cell necrosis. Radical scavengers protected against the formation of DNA strand breaks and inhibition of proinsulin synthesis. Inhibitors of PARP prevented the NAD+ depletion, inhibition of proinsulin synthesis and β-cell death. These findings led to the proposed unifying concept for β-cell damage and its prevention (the Okamoto model). The model met one proof with PARP knockout animals and was further extended by the discovery of cyclic ADP-ribose as the second messenger for Ca2+ mobilization in glucose-induced insulin secretion and by the identification of Reg (Regenerating gene) for β-cell regeneration. Physiological and pathological events found in pancreatic β-cells have been observed in other cells and tissues.</p>
Journal
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- Proceedings of the Japan Academy, Series B
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Proceedings of the Japan Academy, Series B 97 (8), 423-461, 2021-10-11
The Japan Academy
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Details 詳細情報について
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- CRID
- 1390008212404795136
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- NII Article ID
- 130008103156
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- NII Book ID
- AA00785485
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- ISSN
- 13492896
- 03862208
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- NDL BIB ID
- 031762492
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- PubMed
- 34629354
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed