|
 |
|
|||||||
|
|||||||||
Diabetes 51:S462-S473, 2002
© 2002 by the American Diabetes Association, Inc.
Section 6: Beta-Cell Survival |
Recent Advances in the Okamoto Model
The CD38-Cyclic ADP-Ribose Signal System and the Regenerating Gene Protein (Reg)-Reg Receptor System in ß-Cells
From the Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
Twenty years ago, we first proposed our hypothesis on ß-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 ß-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 ß-cell regeneration. The physiological and pathological significance of the two signal systems in a variety of cells and tissues as well as in pancreatic ß-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 ß-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 ß-cell death, PARP and its inhibitors have key roles in the induction of ß-cell regeneration, the maintenance of insulin secretion, and the prevention of ß-cell death.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Shigeto, M. Katsura, M. Matsuda, S. Ohkuma, and K. Kaku Nateglinide and Mitiglinide, but Not Sulfonylureas, Induce Insulin Secretion through a Mechanism Mediated by Calcium Release from Endoplasmic Reticulum J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 1 - 7. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Lu, A. Ponton, H. Okamoto, S. Takasawa, P. L. Herrera, and J.-L. Liu Activation of the Reg family genes by pancreatic-specific IGF-I gene deficiency and after streptozotocin-induced diabetes in mouse pancreas Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E50 - E58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, Y.-G. Chen, P. C. Reifsnyder, W. H. Schott, C.-H. Lee, M. Osborne, F. Scheuplein, F. Haag, F. Koch-Nolte, D. V. Serreze, et al. Targeted Disruption of CD38 Accelerates Autoimmune Diabetes in NOD/Lt Mice by Enhancing Autoimmunity in an ADP-Ribosyltransferase 2-Dependent Fashion. J. Immunol., April 15, 2006; 176(8): 4590 - 4599. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Oshikawa, A. Tanoue, T.-a. Koshimizu, Y. Kitagawa, and G. Tsujimoto Vasopressin Stimulates Insulin Release from Islet Cells through V1b Receptors: a Combined Pharmacological/Knockout Approach Mol. Pharmacol., March 1, 2004; 65(3): 623 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Unno, K. Nata, N. Noguchi, Y. Narushima, T. Akiyama, T. Ikeda, K. Nakagawa, S. Takasawa, and H. Okamoto Production and Characterization of Reg Knockout Mice: Reduced Proliferation of Pancreatic {beta}-Cells in Reg Knockout Mice Diabetes, December 1, 2002; 51(90003): S478 - 483. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |