| Pancreatic beta-cell death, regeneration and insulin secretion: roles of poly(ADP-ribose) polymerase and cyclic ADP-ribose. | |
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MedLine Citation:
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PMID: 11991201 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In the early 1980s, we proposed a unifying model for beta-cell damage (The OKAMOTO model), in which poly(ADP-ribose) synthetase/polymerase (PARP) activation plays an essential role in the consumption of NAD+, which leads to energy depletion and necrotic cell death. In 1984, we demonstrated that the administration of PARP inhibitors to 90% depancreatized rats induces islet regeneration. From the regenerating islet-derived cDNA library we isolated Reg (Regenerating Gene) and demonstrated that Reg protein induces beta-cell replication via the Reg receptor and ameliorates experimental diabetes. More recently, we showed that the combined addition of IL-6 and dexamethasone induces the Reg gene expression in beta-cells and that PARP inhibitors enhance the expression. In 1993, we found that cyclic ADP-ribose (cADPR), a product synthesized from NAD+, is a second messenger for intracellular Ca2+ mobilization for insulin secretion by glucose, and proposed a novel mechanism of insulin secretion, the CD38-cADPR signal system. Therefore, PARP inhibitors prevent beta-cell necrosis, induce beta-cell replication and maintain insulin secretion. |
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Authors:
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Shin Takasawa; Hiroshi Okamoto |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: International journal of experimental diabetes research Volume: 3 ISSN: 1560-4284 ISO Abbreviation: Int. J. Exp. Diabetes Res. Publication Date: 2002 Apr-Jun |
Date Detail:
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Created Date: 2002-05-06 Completed Date: 2002-11-05 Revised Date: 2008-11-20 |
Medline Journal Info:
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Nlm Unique ID: 100962067 Medline TA: Int J Exp Diabetes Res Country: United States |
Other Details:
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Languages: eng Pagination: 79-96 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Death Cyclic ADP-Ribose / metabolism* Humans Insulin / secretion* Islets of Langerhans / cytology*, enzymology, physiology* Poly(ADP-ribose) Polymerases / metabolism* Regeneration / physiology* |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 119340-53-3/Cyclic ADP-Ribose; EC 2.4.2.30/Poly(ADP-ribose) Polymerases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
| Full Text | |
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Journal Information Journal ID (nlm-ta): Int J Exp Diabetes Res ISSN: 1560-4284 Publisher: Hindawi Publishing Corporation |
Article Information Download PDF  Copyright ? 2002 Hindawi Publishing Corporation. open-access: This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Print publication date: Year: 2002 Volume: 3 Issue: 2 First Page: 79 Last Page: 96 ID: 2478571 PubMed Id: 11991201 Publisher Item Identifier: S1687521402000107 DOI: 10.1080/15604280214485 |
| Pancreatic ?-Cell Death, Regeneration and Insulin Secretion: Roles of Poly(ADP-Ribose) Polymerase and Cyclic ADP-Ribose | |
| Shin Takasawa1 | |
| Hiroshi Okamoto1 |
Address: okamotoh@mail.cc.tohoku.ac.jp |
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1Department of BiochemistryTohoku University Graduate School of MedicineSendai980-8575Japan |
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