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Molecular and Cellular Biology, April 2006, p. 2772-2781, Vol. 26, No. 7
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.7.2772-2781.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Selective Deletion of Pten in Pancreatic ß Cells Leads to Increased Islet Mass and Resistance to STZ-Induced Diabetes{dagger}

Bangyan L. Stiles,1* Christine Kuralwalla-Martinez,2 Wei Guo,1 Caroline Gregorian,1 Ying Wang,1 Jide Tian,1 Mark A. Magnuson,3 and Hong Wu1*

Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California,1 Department of Pediatrics, Division of Neonatology, Children's Hospital of Orange County, Orange, California,2 Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee3

Received 12 September 2005/ Returned for modification 12 October 2005/ Accepted 22 December 2005

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a lipid phosphatase. PTEN inhibits the action of phosphatidylinositol-3-kinase and reduces the levels of phosphatidylinositol triphosphate, a crucial second messenger for cell proliferation and survival, as well as insulin signaling. In this study, we deleted Pten specifically in the insulin producing ß cells during murine pancreatic development. Pten deletion leads to increased cell proliferation and decreased cell death, without significant alteration of ß-cell differentiation. Consequently, the mutant pancreas generates more and larger islets, with a significant increase in total ß-cell mass. PTEN loss also protects animals from developing streptozotocin-induced diabetes. Our data demonstrate that PTEN loss in ß cells is not tumorigenic but beneficial. This suggests that modulating the PTEN-controlled signaling pathway is a potential approach for ß-cell protection and regeneration therapies.

* Corresponding author. Mailing address for Hong Wu: Molecular and Medical Pharmacology, UCLA School of Medicine, Los Angeles, CA 90095. Phone: (310) 825-5160. Fax: (310) 825-5454. E-mail: hwu{at}mednet.ucla.edu. Present address for Bangyan Stiles: Molecular Pharmacology and Toxicology, USC School of Pharmacy, Los Angeles, CA 90089. Phone: (323) 442-1417. Fax: (323) 224-7473. E-mail: bstiles{at}pharside2.hsc.usc.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, April 2006, p. 2772-2781, Vol. 26, No. 7
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.7.2772-2781.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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