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 Bell, E. Articles by Wolf, B. A. Search for Related Content PubMed PubMed Citation Articles by Bell, E. Articles by Wolf, B. A. Social Bookmarking                What's this?

Rapamycin Has a Deleterious Effect on MIN-6 Cells and Rat and Human Islets

¹ Department of Pathology and Laboratory Medicine, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania
² Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
³ Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Rapamycin (sirolimus) is a macrolide fungicide with immunosuppressant properties that is used in human islet transplantation. Little is known about the effects of rapamycin on MIN-6 cells and islets. Rapamycin had a dose-dependent, time-dependent, and glucose-independent deleterious effect on MIN-6 cell viability. At day 1, using the MTT method, 0.01 nmol/l rapamycin reduced cell viability to 83 ± 6% of control (P < 0.05). Using the calcein AM method, at day 2, 10 nmol/l rapamycin caused a reduction in cell viability to 73 ± 5% of control (P < 0.001). Furthermore, 10 and 100 nmol/l rapamycin caused apoptosis in MIN-6 cells as assessed by the transferase-mediated dUTP nick-end labeling assay. Compared with control, there was a 3.1 ± 0.6-fold increase (P < 0.01) in apoptosis in MIN-6 cells treated with 10 nmol/l rapamycin. A supra-therapeutic rapamycin concentration of 100 nmol/l significantly impaired glucose- and carbachol-stimulated insulin secretion in rat islets and had a deleterious effect on the viability of rat and human islets, causing apoptosis of both - and ß-cells.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				D. Su, N. Zhang, J. He, S. Qu, S. Slusher, R. Bottino, S. Bertera, J. Bromberg, and H. H. Dong Angiopoietin-1 Production in Islets Improves Islet Engraftment and Protects Islets From Cytokine-Induced Apoptosis Diabetes, September 1, 2007; 56(9): 2274 - 2283. [Abstract] [Full Text] [PDF]

				M. Krebs, B. Brunmair, A. Brehm, M. Artwohl, J. Szendroedi, P. Nowotny, E. Roth, C. Furnsinn, M. Promintzer, C. Anderwald, et al. The Mammalian Target of Rapamycin Pathway Regulates Nutrient-Sensitive Glucose Uptake in Man Diabetes, June 1, 2007; 56(6): 1600 - 1607. [Abstract] [Full Text] [PDF]

				N. Zhang, D. Su, S. Qu, T. Tse, R. Bottino, A.N. Balamurugan, J. Xu, J. S. Bromberg, and H. H. Dong Sirolimus Is Associated With Reduced Islet Engraftment and Impaired {beta}-Cell Function Diabetes, September 1, 2006; 55(9): 2429 - 2436. [Abstract] [Full Text] [PDF]

				I. Tancevski, A. Wehinger, W. Schgoer, P. Eller, S. Cuzzocrea, B. Foeger, J. R. Patsch, and A. Ritsch Aspirin regulates expression and function of scavenger receptor-BI in macrophages: studies in primary human macrophages and in mice FASEB J, July 1, 2006; 20(9): 1328 - 1335. [Abstract] [Full Text] [PDF]

				E. A. Ryan, B. W. Paty, P. A. Senior, D. Bigam, E. Alfadhli, N. M. Kneteman, J. R.T. Lakey, and A.M. J. Shapiro Five-Year Follow-Up After Clinical Islet Transplantation Diabetes, July 1, 2005; 54(7): 2060 - 2069. [Abstract] [Full Text] [PDF]

				H. Chen, X. Li, and P. N. Epstein MnSOD and Catalase Transgenes Demonstrate That Protection of Islets From Oxidative Stress Does Not Alter Cytokine Toxicity Diabetes, May 1, 2005; 54(5): 1437 - 1446. [Abstract] [Full Text] [PDF]

				H. Hui, N. Khoury, X. Zhao, L. Balkir, E. D'Amico, A. Bullotta, E. D. Nguyen, A. Gambotto, and R. Perfetti Adenovirus-Mediated XIAP Gene Transfer Reverses the Negative Effects of Immunosuppressive Drugs on Insulin Secretion and Cell Viability of Isolated Human Islets Diabetes, February 1, 2005; 54(2): 424 - 433. [Abstract] [Full Text] [PDF]

				B. Schroppel, N. Zhang, P. Chen, D. Chen, J. S. Bromberg, and B. Murphy Role of Donor-Derived Monocyte Chemoattractant Protein-1 in Murine Islet Transplantation J. Am. Soc. Nephrol., February 1, 2005; 16(2): 444 - 451. [Abstract] [Full Text] [PDF]

				M. R. Rickels, M. H. Schutta, J. F. Markmann, C. F. Barker, A. Naji, and K. L. Teff {beta}-Cell Function Following Human Islet Transplantation for Type 1 Diabetes Diabetes, January 1, 2005; 54(1): 100 - 106. [Abstract] [Full Text] [PDF]

				J. L. Larsen Pancreas Transplantation: Indications and Consequences Endocr. Rev., December 1, 2004; 25(6): 919 - 946. [Abstract] [Full Text] [PDF]