This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zeender, E. Articles by Halban, P. A. Search for Related Content PubMed PubMed Citation Articles by Zeender, E. Articles by Halban, P. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB GLUCOSE NITRIC OXIDE

Pioglitazone and Sodium Salicylate Protect Human ß-Cells against Apoptosis and Impaired Function Induced by Glucose and Interleukin-1ß

Department of Genetic Medicine and Development (E.Z., P.A.H.), University Medical Centre and Division of Surgical Research (E.Z., T.B., D.B.), Department of Surgery, University Hospital, Geneva CH-1211, Switzerland; and Division of Endocrinology and Diabetes (K.M., M.Y.D.), University Hospital, Zurich CH-8091, Switzerland

Address all correspondence and requests for reprints to: Philippe A. Halban, Department of Genetic Medicine and Development, University Medical Center, 1 rue Michel-Servet, 1211 Geneva 4, Switzerland. E-mail: philippe.halban{at}medecine.unige.ch.

Decreased functional ß-cell mass in type 1 and type 2 diabetes is due to ß-cell apoptosis and impaired secretory function suggested to be mediated, in part, by immune- and/or high-glucose-induced production of IL-1ß acting through the nuclear factor B (NFB)/Fas pathway. The aim of this study was to determine whether two drugs believed to block NFB activation, the thiazolidinedione (glitazone) pioglitazone and the nonsteroidal antiinflammatory drug sodium salicylate, can protect human ß-cells against the toxic effects of IL-1ß and high glucose in vitro. Human islets were maintained in culture 2–4 d at 100 mg/dl (5.5 mM) glucose with or without (control) IL-1ß or at 600 mg/dl (33.3 mM) glucose. IL-1ß and 600 mg/dl glucose increased ß-cell apoptosis and abolished short-term glucose-stimulated insulin secretion. Both drugs protected partially against loss of glucose-stimulated insulin secretion and prevented completely increased apoptosis caused by IL-1ß or 600 mg/dl glucose. IL-1ß secretion from islets was increased by 4-d culture at 600 mg/dl, and this was blocked by pioglitazone. Both drugs prevented activation of ß-cell NFB by high glucose. Pioglitazone and sodium salicylate thus protect human islets against the detrimental effects of IL-1ß and high glucose by blocking NFB activation and may therefore be useful in retarding the manifestation and progression of diabetes.

This article has been cited by other articles:

				M. Y. Donath, D. M. Schumann, M. Faulenbach, H. Ellingsgaard, A. Perren, and J. A. Ehses Islet Inflammation in Type 2 Diabetes: From metabolic stress to therapy Diabetes Care, February 1, 2008; 31(Supplement_2): S161 - S164. [Abstract] [Full Text] [PDF]

				B. Yermen, A. Tomas, and P. A. Halban Pro-Survival Role of Gelsolin in Mouse {beta}-Cells Diabetes, January 1, 2007; 56(1): 80 - 87. [Abstract] [Full Text] [PDF]

				R. J Deckelbaum, T. S Worgall, and T. Seo n-3 Fatty acids and gene expression Am. J. Clinical Nutrition, June 1, 2006; 83(6): S1520 - 1525S. [Abstract] [Full Text] [PDF]

				R. A. Ritzel, A. E. Butler, R. A. Rizza, J. D. Veldhuis, and P. C. Butler Relationship Between {beta}-Cell Mass and Fasting Blood Glucose Concentration in Humans. Diabetes Care, March 1, 2006; 29(3): 717 - 718. [Full Text] [PDF]

				C.-Y. Lin, T. Gurlo, L. Haataja, W. A. Hsueh, and P. C. Butler Activation of Peroxisome Proliferator-Activated Receptor-{gamma} by Rosiglitazone Protects Human Islet Cells against Human Islet Amyloid Polypeptide Toxicity by a Phosphatidylinositol 3'-Kinase-Dependent Pathway J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6678 - 6686. [Abstract] [Full Text] [PDF]

				M. Y. Donath, J. A. Ehses, K. Maedler, D. M. Schumann, H. Ellingsgaard, E. Eppler, and M. Reinecke Mechanisms of {beta}-Cell Death in Type 2 Diabetes Diabetes, December 1, 2005; 54(suppl_2): S108 - S113. [Abstract] [Full Text] [PDF]

				E. B. Hammar, J.-C. Irminger, K. Rickenbach, G. Parnaud, P. Ribaux, D. Bosco, D. G. Rouiller, and P. A. Halban Activation of NF-{kappa}B by Extracellular Matrix Is Involved in Spreading and Glucose-stimulated Insulin Secretion of Pancreatic Beta Cells J. Biol. Chem., August 26, 2005; 280(34): 30630 - 30637. [Abstract] [Full Text] [PDF]