HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gonzalez, C. Articles by Lévi-Strauss, M. Search for Related Content PubMed PubMed Citation Articles by Gonzalez, C. Articles by Lévi-Strauss, M. Social Bookmarking                What's this?

Unexpected Sensitivity of Nonobese Diabetic Mice With a Disrupted Poly(ADP-Ribose) Polymerase-1 Gene to Streptozotocin-Induced and Spontaneous Diabetes

¹ Institut National de la Santé et de la Recherche Médicale, Unité 25, Hôpital Necker, Paris, France
² Centre National de la Recherche Scientifique, Ecole Supérieure de Biotechnologie de Strasbourg, Illkirch, France
³ Sanofi-Synthélabo Recherche, Département Cardio-Vasculaire, Chilly Mazarin Cedex, France

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme that consumes NAD in response to DNA strand breaks. Its excessive activation seems particularly deleterious to pancreatic ß-cells, as exemplified by the complete resistance of PARP-1-deficient mice to the toxic diabetes induced by streptozotocin. Because of the possible implication of this enzyme in type 1 diabetes, many human trials using nicotinamide, an inhibitor of PARP-1, have been conducted either in patients recently diagnosed or in subjects highly predisposed to this disease. To analyze the role of this enzyme in murine type 1 diabetes, we introgressed a disrupted PARP-1 allele onto the autoimmune diabetes-prone nonobese diabetic (NOD) mouse strain. We showed that these mice were protected neither from spontaneous nor from cyclophosphamide-accelerated diabetes. Surprisingly they were also highly sensitive to the diabetes induced by a single high dose of streptozotocin, standing in sharp contrast with C57BL/6 mice that bear the same inactivated PARP-1 allele. Our results suggest that NOD mice are characterized not only by their immune dysfunction but also by a peculiarity of their islets leading to a PARP-1-independent mechanism of streptozotocin-induced ß-cell death.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				A. P. W. Johnston, J. E. Campbell, J. G. Found, M. C. Riddell, and T. J. Hawke Streptozotocin induces G2 arrest in skeletal muscle myoblasts and impairs muscle growth in vivo Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1033 - C1040. [Abstract] [Full Text] [PDF]

				W. L. Suarez-Pinzon, J. G. Mabley, R. Power, C. Szabo, and A. Rabinovitch Poly (ADP-Ribose) Polymerase Inhibition Prevents Spontaneous and Recurrent Autoimmune Diabetes in NOD Mice by Inducing Apoptosis of Islet-Infiltrating Leukocytes Diabetes, July 1, 2003; 52(7): 1683 - 1688. [Abstract] [Full Text] [PDF]

				L. Virag and C. Szabo The Therapeutic Potential of Poly(ADP-Ribose) Polymerase Inhibitors Pharmacol. Rev., September 1, 2002; 54(3): 375 - 429. [Abstract] [Full Text] [PDF]